- Email: [email protected]
p130 and ER-β in MCF-7 breast cancer cells
symposium article
Annals of Oncology 17 (Supplement 7): vii27–vii29, 2006 doi:10.1093/annonc/mdl945
Nuclear and cytoplasmic interaction of pRb2/p130 and ER-b in MCF-7 breast cancer cells M. Macaluso1,2,3, M. Montanari1,2, P. B. Noto1, V. Gregorio1,3, E. Surmacz1 & A. Giordano1,2* 2
Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA; Department of Human Pathology and Oncology University of Siena, Siena, Italy; 3Section of Oncology, Department of Oncology; University of Palermo, Palermo, Italy
introduction Estrogens have many cellular functions in mammals including, but not limited to, reproduction, skeletal homeostasis, cardiovascular and central nervous system health, and lipid metabolism [1]. Moreover, it has been reported that estrogens also influence the pathological processes of hormone-dependent diseases, such as breast, endometrial and ovarian cancers, as well as osteoporosis [1–3]. Several different mechanisms mediate the action of estrogens and central to these mechanisms is their interactions with estrogen receptors a and b (ER-a and ER-b) [4, 5]. ER-a and its ligand 17b-estradiol (E2) play a crucial role in normal breast development and have also been linked to mammary carcinogenesis and clinical outcome in breast cancer patients [2, 6]. Many studies have been reported that neoplastic cells can express a variety of receptors, whose presence can provide a means for controlling cell growth through chemotherapeutic agents [2, 7, 8]. The hormone receptor status (ER-a, progesterone receptor PgR) of the breast cancer cells may represent a predictor of response to hormonal therapies [7]. ER-b seems to play a different role in breast tumorigenesis than ER-a [9, 10]. In addition, decreased expression of ER-b has been observed in prostatic, lung and colorectal cancers *Correspondence to: A. Giordano, Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, 19122-Philadelphia, PA, USA. Tel: +1-215-204-9520; Fax: +1-215-204-9519; E-mail: [email protected]
ª 2006 European Society for Medical Oncology
[11–13]. ER-b is structurally similar to ER-a with the least homology in the AF-1 domain. While ER-b is abundant in normal mammary gland, its expression appears to be reduced during carcinogenesis [14]. Interestingly, it has been reported that ER-b expression could be induced by tamoxifen and certain estrogens, such as phytoestrogens, which may work as antioxidants indicating that ER-b could be involved in the control of antioxidant-regulated genes [15, 16]. Several types of splicing variants of ER-b have been reported to date [9, 17]. The ER-bcx variant, which is truncated at the COOH terminus, has been found to be expressed in the ovary, prostate, testis and thymus [18–20]. ER-bcx preferentially forms heterodimers with ER-a and ER-b and may have a dominant-negative effect on ER-a function [21]. Interestingly, it has been suggested that ER-bcx expression in breast cancer could modulate the response to antiestrogens in cells coexpressing and, thus, influence clinical outcome [21]. Previously, we have reported that pRb2/p130, retinoblastoma related protein, in association with chromatin remodeling enzymes, binds to the ER-a promoter in breast cancer cells. On the contrary, no binding was detected between pRb2/p130 and ER-b gene [22]. Here, we report for the first time a cytoplasmic and nuclear interaction between ER-b and pRb2/p130 proteins in both nucleus and cytoplasm of MCF-7 breast cancer cells. Our hypothesis is that pRb2/130 could influence the shuttle of ER-b between these cellular compartments. Moreover, we
Downloaded from http://annonc.oxfordjournals.org/ at Ritsumeikan University on June 6, 2015
Estrogens exhibit important biological functions and influence several pathological processes of hormonedependent diseases. The biological actions of estrogens require their interaction with two estrogen receptors (ER-a and ER-b), which are ligand-dependent transcription factors. ER-a and ER-b exhibit distinct tissue expression patterns as well as show different patterns of gene regulation. In addition, it has been suggested that ER-b works as a counter partner of ER-a through inhibition of the transactivating functions of ER-a. For instance, ER-b seems to play a different role in breast tumorigenesis than ER-a, as ER-b decreased expression in breast cancer has been correlated with bad prognosis. Biological activities of ER-a and ER-b could be controlled by a number of interacting proteins such as activators/inhibitors, ligand binding and kinases. We have previously reported that pRb2/p130, retinoblastoma related protein, could be involved in the silencing of ER-a gene during breast tumorigenesis. Here, we report that ER-b and pRb2/p130 proteins co-immunoprecipitate in both nucleus and cytoplasm of MCF-7 breast cancer cells. Our hypothesis is that the interaction of pRb2/130 with ER-b may have a functional significance in regulating ER-b activity. Key words: estrogens, estrogen receptors, pRb2/130, breast cancer
symposium article
1
symposium article suggest that the interaction of pRb2/130 with ER-b may have a functional significance in regulating ER-b heterodimerization.
Annals of Oncology
ER-b may have a functional significance in regulating the ER-b heterodimerization.
conclusions methods and results pRb2/130 and ER-b proteins co-immunoprecipitate in the cytoplasm and nucleus of MCF-7 breast cancer cells
Figure 1. ER-b coimmunoprecipitates with pRb2/p130 in MCF-7 cells. Immunoprecipitation of pRb2/p130 from cytoplasm (IP pRb2/p130 cytoplasmic fraction) and nuclear (IP pRb2/p130 nuclear fraction) fractions from MCF-7 cells by using an anti-pRb2/p130 antibody, followed by electrophoresis and Western blotting of the immunoprecipitates with anti-ER-b antibody. Control (lane 1) represents Western blotting of nuclear or cytoplasmic immunoprecipitates where the anti-pRb2/p130 antibody was omitted. The purity of cytoplasmic and nuclear fractions was assessed by immunoblot analysis using anti-GAPDH as cytoplasmic marker and anti-Oct1 as nuclear marker.
vii28 | Macaluso et al.
Volume 17 | Supplement 7 | June 2006
Downloaded from http://annonc.oxfordjournals.org/ at Ritsumeikan University on June 6, 2015
Cytoplasmic and nuclear proteins were extracted from MCF-7 cells, which were cultured according to the manufacturer’s protocols, by using the PARIS kit (Ambion). Efficient cytoplasmic and nuclear fractionation was confirmed by Western blotting analysis using anti-GAPDH antibody for cytoplasmic fraction and anti Oct-1 antibody for nuclear fraction. Immunoprecipitations experiments were performed from cytoplasmic and nuclear fractions and using pRb2/130 as immunoprecipitating antibody (211.6, Santa Cruz Biotechnology, CA) (Figure 1). The presence of ER-b in both pRb2/130 nuclear and cytoplasmic precipitates was assessed with a rabbit polyclonal antibody that recognizes the NH2-terminal region of ER-b (YAEPQKSPWCEARSLEHT; Upstate) by Western blotting (Figure 1). In addition, as expected, the anti-pRb2/130 antibody immunoprecipitated pRb2/130 from both nuclear and cytoplasmic fractions of all the cell lines (data not shown). For Western blotting, proteins were size fractionated by SDS-PAGE, transferred to nitrocellulose and probed with anti-ER-b antibody (1:400). Proteins were visualized using a goat anti-rabbit secondary antibody conjugated to HRP and antibody staining was detected using the enhanced chemiluminescence visualization system (ECL; Amersham Pharmacia Biotech) according to the manufacturer’s instructions. The results were confirmed by performing immunoprecipitations from cytoplasmic and nuclear fractions of MCF-7 cells, and using anti-ER-b as immunoprecipitating antibody. The immunoprecipitates were then analyzed by Western blotting using anti-pRb2/p130 antibody (data not shown). Our results indicate that pRb2/p130 and ER-b proteins coimmunoprecipitate in the cytoplasm and nucleus of MCF-7 breast cancer cells (Figure 1). We postulate that pRb2/p130 and ER-b could be involved in a common mechanism influencing the shuttle of ER-b between these cellular compartments. In addition, the interaction of pRb2/p130 with
In addition to proliferative effects on normal cells, estrogen stimulates the initiation and promotion of tumors [1]. Both clinical and animal studies have been indicated that loss of estrogen or its receptor(s) contributes to the development or progression of various diseases [1, 7] For instance, estrogen plays a crucial role in proliferation of cancer cells in reproductive organs such as the breast and the uterus [23–25]. The estrogen-stimulated growth requires the estrogen receptor (ER), which are ligand-dependent transcription factors. ER-a and ER-b represent distinct gene products and share similar structure and modes of action [26]. However, many studies have been indicated that ER-a and ER-b have distinct tissue expression patterns both in human and in rodents as well as exhibit different physiological effects in the reproductive system, bone, cardiovascular system, hematopoiesis, and central and peripheral nervous systems [26, 1]. Biological activities of ER-a and ER-b could be controlled by a number of interacting proteins. It has been suggested that ER-b works as a counter partner of ER-a through inhibition of the transactivating functions of ER-a by heterodimerization as well as by ER-b-specific regulated genes, which are probably related to its anti-proliferative properties [9]. We have previously reported that pRb2/p130, retinoblastoma related protein, in association with chromatin remodeling enzymes, binds to the ER-a promoter and could be involved in the silencing of this gene during breast tumorigenesis. Moreover, we have also indicated that no binding was detected between pRb2/p130 and ER-b gene [22]. Here, we report that ER-b and pRb2/p130 proteins coimmunoprecipitate in both nucleus and cytoplasm of MCF-7 breast cancer cells. Our hypothesis is that the interaction of pRb2/130 with ER-b may have a functional significance in regulating ER-b activity.
Annals of Oncology
acknowledgements This study was supported by NIH grants, Sbarro Health Research Organization (www.shro.org) and A.I.R.C. (Associazione Italiana per la Ricerca sul Cancro) to Antonio Giordano. Dr Micaela Montanari acknowledges Cava Oggi Foundation. Dr Marcella Macaluso is supported by a F.I.R.C. (Fondazione Italiana per la Ricerca sul Cancro) fellowship.
references
Volume 17 | Supplement 7 | June 2006
11. Ji Q, Liu PI, Elshimali Y et al. Frequent loss of estrogen and progesterone receptors in human prostatic tumors determined by quantitative real-time PCR. Mol Cell Endocrinol 2005; 229: 103–110. 12. Kawai H, Ishii A, Washiya K et al. Estrogen receptor alpha and beta are prognostic factors in non-small cell lung cancer. Clin Cancer Res. 2005; 11(14): 5084–5089. 13. Jassam N, Bell SM, Speirs V et al. Loss of expression of oestrogen receptor beta in colon cancer and its association with Dukes’ staging. Oncol Rep 2005; 14: 17–21. 14. Macaluso M, Montanari M, Giordano A. The regulation of Er-a transcription by pRb2/p130 in breast cancer. Ann Oncol 2005; Suppl 4: iv20–iv22. 15. Gustafsson J-A. Estrogen receptor-b a new dimension in estrogen mechanism of action. J Endocrinol 1999; 163: 379–383. 16. Usui T. Pharmaceutical prospect of phytoestrogens. Endocrine J 2006; 53: 7–20. 17. Speirs V, Carder PJ, Lane S et al. Oestrogen receptor beta: what means for patients with breast cancer. Lancet Oncol 2004; 5: 174–180. 18. Ogawa S, Inoue S, Watanabe T et al. Molecular cloning and characterization of human estrogen receptor bcx: a potential inhibitor of estrogen action in human. Nucleic Acid Res 1998; 26: 3505–3512. 19. Adams JY, Leav I, Lau KM et al. Expression of estrogen beta in the fetal, neonatal, and prepubertal human prostate. Prostate 2002; 52: 69–81. 20. Scobie GA, MacPherson S, Millar MR et al. Human oestrogen receptors: differential expression of ER-a and b and the identification of ER-b variants. Steroids 2002; 67: 985–992. 21. Palmieri C, Lam EW-F, Mansi J et al. The expression of ERbcx in human breast cancer and the relationship to endocrine therapy and survival. Clin Canc Res 2004; 10: 2421–2428. 22. Macaluso M, Cinti C, Russo G et al. pRb2/p130-E2F4/5-HDAC1-SUV39H1DNMT1 multimolecular complexes mediate the transcription of Estrogen Receptor-a in breast cancer. Oncogene 2003; 22: 3511–3517. 23. Song RX, Santen RJ. Membrane initiated estrogen signaling in breast cancer. Biol Reprod 2006; ?: 000–000. 24. Wallace OB, Lauwers KS, Dodge JA et al. A selective estrogen receptor modulator for the treatment of hot flushes. J Med Chem 2006; 49: 843–846. 25. Nair HB, Luthra R, Kirma N et al. Induction of aromatase expression in cervical carcinomas: effects of endogenous estrogen on cervical cancer cell proliferation. Cancer Res 2005; 65: 11164–11173. 26. Ikeda K, Inoue S. Estrogen receptors and their downstream targets in cancer. Arch Histol Cytol 2004; 67: 435–442.
doi:10.1093/annonc/mdl945 | vii29
Downloaded from http://annonc.oxfordjournals.org/ at Ritsumeikan University on June 6, 2015
1. Deroo BJ, Korach KS. Estrogen receptors and human diseases. J Clin Invest 2006; 116: 561–570. 2. Normanno N, Di Maio M, De Maio E et al. Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer. Endocr-Relat Cancer 2005; 12: 721–747. 3. Reginster JY, Devogelaer JP. Raloxifene reduces fractures in postmenopausal women with osteoporosis. Clin Orthop Relat Res 2006; 443: 48–54. 4. Huang J, Li X, Hilf R et al. Molecular basis of therapeutic strategies for breast cancer. Curr Drug Targets Immune Endocr Metabol Disord 2005; 5: 379–396. 5. Gururaj AE, Rayala SK, Vadlamudi RK et al. Novel mechanisms of resistance to endocrine therapy: genomic and nongenomic considerations. Clin Cancer Res 2006; 12 (3 Pt2): 1001s–1007s. 6. Leclercq G, Lacroix M, Laios I et al. Estrogen receptor alpha: impact of ligands on intracellular shuttling and turnover rate in breast cancer cells. Curr Cancer Drug Targets 2006; 6: 39–64. 7. Houssami N, Cuzick J, Dixon JM. The prevention, detection and management of breast cancer. Med J Aust 2006; 184: 230–234. 8. Lim SC. CD24 and human carcinoma: tumor biological aspects. Biomed Pharmacother 2005; 59 (Suppl 2): S351–354. 9. Saji S, Hirose M, Toi M. Clinical significance of estrogen receptor bin breast cancer. Cancer Chemother Pharmacol 2005; 56 (Suppl 1): s21–s26. 10. Leygue E, Dotzlaw H, Watson PH, Murphy LC. Altered estrogen receptor a and b messenger RNA expression during human breast tumorigenesis. Cancer Res 1998; 58: 3197–3200.
symposium article
Annals of Oncology 17 (Supplement 7): vii27–vii29, 2006 doi:10.1093/annonc/mdl945
Nuclear and cytoplasmic interaction of pRb2/p130 and ER-b in MCF-7 breast cancer cells M. Macaluso1,2,3, M. Montanari1,2, P. B. Noto1, V. Gregorio1,3, E. Surmacz1 & A. Giordano1,2* 2
Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA; Department of Human Pathology and Oncology University of Siena, Siena, Italy; 3Section of Oncology, Department of Oncology; University of Palermo, Palermo, Italy
introduction Estrogens have many cellular functions in mammals including, but not limited to, reproduction, skeletal homeostasis, cardiovascular and central nervous system health, and lipid metabolism [1]. Moreover, it has been reported that estrogens also influence the pathological processes of hormone-dependent diseases, such as breast, endometrial and ovarian cancers, as well as osteoporosis [1–3]. Several different mechanisms mediate the action of estrogens and central to these mechanisms is their interactions with estrogen receptors a and b (ER-a and ER-b) [4, 5]. ER-a and its ligand 17b-estradiol (E2) play a crucial role in normal breast development and have also been linked to mammary carcinogenesis and clinical outcome in breast cancer patients [2, 6]. Many studies have been reported that neoplastic cells can express a variety of receptors, whose presence can provide a means for controlling cell growth through chemotherapeutic agents [2, 7, 8]. The hormone receptor status (ER-a, progesterone receptor PgR) of the breast cancer cells may represent a predictor of response to hormonal therapies [7]. ER-b seems to play a different role in breast tumorigenesis than ER-a [9, 10]. In addition, decreased expression of ER-b has been observed in prostatic, lung and colorectal cancers *Correspondence to: A. Giordano, Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, 19122-Philadelphia, PA, USA. Tel: +1-215-204-9520; Fax: +1-215-204-9519; E-mail: [email protected]
ª 2006 European Society for Medical Oncology
[11–13]. ER-b is structurally similar to ER-a with the least homology in the AF-1 domain. While ER-b is abundant in normal mammary gland, its expression appears to be reduced during carcinogenesis [14]. Interestingly, it has been reported that ER-b expression could be induced by tamoxifen and certain estrogens, such as phytoestrogens, which may work as antioxidants indicating that ER-b could be involved in the control of antioxidant-regulated genes [15, 16]. Several types of splicing variants of ER-b have been reported to date [9, 17]. The ER-bcx variant, which is truncated at the COOH terminus, has been found to be expressed in the ovary, prostate, testis and thymus [18–20]. ER-bcx preferentially forms heterodimers with ER-a and ER-b and may have a dominant-negative effect on ER-a function [21]. Interestingly, it has been suggested that ER-bcx expression in breast cancer could modulate the response to antiestrogens in cells coexpressing and, thus, influence clinical outcome [21]. Previously, we have reported that pRb2/p130, retinoblastoma related protein, in association with chromatin remodeling enzymes, binds to the ER-a promoter in breast cancer cells. On the contrary, no binding was detected between pRb2/p130 and ER-b gene [22]. Here, we report for the first time a cytoplasmic and nuclear interaction between ER-b and pRb2/p130 proteins in both nucleus and cytoplasm of MCF-7 breast cancer cells. Our hypothesis is that pRb2/130 could influence the shuttle of ER-b between these cellular compartments. Moreover, we
Downloaded from http://annonc.oxfordjournals.org/ at Ritsumeikan University on June 6, 2015
Estrogens exhibit important biological functions and influence several pathological processes of hormonedependent diseases. The biological actions of estrogens require their interaction with two estrogen receptors (ER-a and ER-b), which are ligand-dependent transcription factors. ER-a and ER-b exhibit distinct tissue expression patterns as well as show different patterns of gene regulation. In addition, it has been suggested that ER-b works as a counter partner of ER-a through inhibition of the transactivating functions of ER-a. For instance, ER-b seems to play a different role in breast tumorigenesis than ER-a, as ER-b decreased expression in breast cancer has been correlated with bad prognosis. Biological activities of ER-a and ER-b could be controlled by a number of interacting proteins such as activators/inhibitors, ligand binding and kinases. We have previously reported that pRb2/p130, retinoblastoma related protein, could be involved in the silencing of ER-a gene during breast tumorigenesis. Here, we report that ER-b and pRb2/p130 proteins co-immunoprecipitate in both nucleus and cytoplasm of MCF-7 breast cancer cells. Our hypothesis is that the interaction of pRb2/130 with ER-b may have a functional significance in regulating ER-b activity. Key words: estrogens, estrogen receptors, pRb2/130, breast cancer
symposium article
1
symposium article suggest that the interaction of pRb2/130 with ER-b may have a functional significance in regulating ER-b heterodimerization.
Annals of Oncology
ER-b may have a functional significance in regulating the ER-b heterodimerization.
conclusions methods and results pRb2/130 and ER-b proteins co-immunoprecipitate in the cytoplasm and nucleus of MCF-7 breast cancer cells
Figure 1. ER-b coimmunoprecipitates with pRb2/p130 in MCF-7 cells. Immunoprecipitation of pRb2/p130 from cytoplasm (IP pRb2/p130 cytoplasmic fraction) and nuclear (IP pRb2/p130 nuclear fraction) fractions from MCF-7 cells by using an anti-pRb2/p130 antibody, followed by electrophoresis and Western blotting of the immunoprecipitates with anti-ER-b antibody. Control (lane 1) represents Western blotting of nuclear or cytoplasmic immunoprecipitates where the anti-pRb2/p130 antibody was omitted. The purity of cytoplasmic and nuclear fractions was assessed by immunoblot analysis using anti-GAPDH as cytoplasmic marker and anti-Oct1 as nuclear marker.
vii28 | Macaluso et al.
Volume 17 | Supplement 7 | June 2006
Downloaded from http://annonc.oxfordjournals.org/ at Ritsumeikan University on June 6, 2015
Cytoplasmic and nuclear proteins were extracted from MCF-7 cells, which were cultured according to the manufacturer’s protocols, by using the PARIS kit (Ambion). Efficient cytoplasmic and nuclear fractionation was confirmed by Western blotting analysis using anti-GAPDH antibody for cytoplasmic fraction and anti Oct-1 antibody for nuclear fraction. Immunoprecipitations experiments were performed from cytoplasmic and nuclear fractions and using pRb2/130 as immunoprecipitating antibody (211.6, Santa Cruz Biotechnology, CA) (Figure 1). The presence of ER-b in both pRb2/130 nuclear and cytoplasmic precipitates was assessed with a rabbit polyclonal antibody that recognizes the NH2-terminal region of ER-b (YAEPQKSPWCEARSLEHT; Upstate) by Western blotting (Figure 1). In addition, as expected, the anti-pRb2/130 antibody immunoprecipitated pRb2/130 from both nuclear and cytoplasmic fractions of all the cell lines (data not shown). For Western blotting, proteins were size fractionated by SDS-PAGE, transferred to nitrocellulose and probed with anti-ER-b antibody (1:400). Proteins were visualized using a goat anti-rabbit secondary antibody conjugated to HRP and antibody staining was detected using the enhanced chemiluminescence visualization system (ECL; Amersham Pharmacia Biotech) according to the manufacturer’s instructions. The results were confirmed by performing immunoprecipitations from cytoplasmic and nuclear fractions of MCF-7 cells, and using anti-ER-b as immunoprecipitating antibody. The immunoprecipitates were then analyzed by Western blotting using anti-pRb2/p130 antibody (data not shown). Our results indicate that pRb2/p130 and ER-b proteins coimmunoprecipitate in the cytoplasm and nucleus of MCF-7 breast cancer cells (Figure 1). We postulate that pRb2/p130 and ER-b could be involved in a common mechanism influencing the shuttle of ER-b between these cellular compartments. In addition, the interaction of pRb2/p130 with
In addition to proliferative effects on normal cells, estrogen stimulates the initiation and promotion of tumors [1]. Both clinical and animal studies have been indicated that loss of estrogen or its receptor(s) contributes to the development or progression of various diseases [1, 7] For instance, estrogen plays a crucial role in proliferation of cancer cells in reproductive organs such as the breast and the uterus [23–25]. The estrogen-stimulated growth requires the estrogen receptor (ER), which are ligand-dependent transcription factors. ER-a and ER-b represent distinct gene products and share similar structure and modes of action [26]. However, many studies have been indicated that ER-a and ER-b have distinct tissue expression patterns both in human and in rodents as well as exhibit different physiological effects in the reproductive system, bone, cardiovascular system, hematopoiesis, and central and peripheral nervous systems [26, 1]. Biological activities of ER-a and ER-b could be controlled by a number of interacting proteins. It has been suggested that ER-b works as a counter partner of ER-a through inhibition of the transactivating functions of ER-a by heterodimerization as well as by ER-b-specific regulated genes, which are probably related to its anti-proliferative properties [9]. We have previously reported that pRb2/p130, retinoblastoma related protein, in association with chromatin remodeling enzymes, binds to the ER-a promoter and could be involved in the silencing of this gene during breast tumorigenesis. Moreover, we have also indicated that no binding was detected between pRb2/p130 and ER-b gene [22]. Here, we report that ER-b and pRb2/p130 proteins coimmunoprecipitate in both nucleus and cytoplasm of MCF-7 breast cancer cells. Our hypothesis is that the interaction of pRb2/130 with ER-b may have a functional significance in regulating ER-b activity.
Annals of Oncology
acknowledgements This study was supported by NIH grants, Sbarro Health Research Organization (www.shro.org) and A.I.R.C. (Associazione Italiana per la Ricerca sul Cancro) to Antonio Giordano. Dr Micaela Montanari acknowledges Cava Oggi Foundation. Dr Marcella Macaluso is supported by a F.I.R.C. (Fondazione Italiana per la Ricerca sul Cancro) fellowship.
references
Volume 17 | Supplement 7 | June 2006
11. Ji Q, Liu PI, Elshimali Y et al. Frequent loss of estrogen and progesterone receptors in human prostatic tumors determined by quantitative real-time PCR. Mol Cell Endocrinol 2005; 229: 103–110. 12. Kawai H, Ishii A, Washiya K et al. Estrogen receptor alpha and beta are prognostic factors in non-small cell lung cancer. Clin Cancer Res. 2005; 11(14): 5084–5089. 13. Jassam N, Bell SM, Speirs V et al. Loss of expression of oestrogen receptor beta in colon cancer and its association with Dukes’ staging. Oncol Rep 2005; 14: 17–21. 14. Macaluso M, Montanari M, Giordano A. The regulation of Er-a transcription by pRb2/p130 in breast cancer. Ann Oncol 2005; Suppl 4: iv20–iv22. 15. Gustafsson J-A. Estrogen receptor-b a new dimension in estrogen mechanism of action. J Endocrinol 1999; 163: 379–383. 16. Usui T. Pharmaceutical prospect of phytoestrogens. Endocrine J 2006; 53: 7–20. 17. Speirs V, Carder PJ, Lane S et al. Oestrogen receptor beta: what means for patients with breast cancer. Lancet Oncol 2004; 5: 174–180. 18. Ogawa S, Inoue S, Watanabe T et al. Molecular cloning and characterization of human estrogen receptor bcx: a potential inhibitor of estrogen action in human. Nucleic Acid Res 1998; 26: 3505–3512. 19. Adams JY, Leav I, Lau KM et al. Expression of estrogen beta in the fetal, neonatal, and prepubertal human prostate. Prostate 2002; 52: 69–81. 20. Scobie GA, MacPherson S, Millar MR et al. Human oestrogen receptors: differential expression of ER-a and b and the identification of ER-b variants. Steroids 2002; 67: 985–992. 21. Palmieri C, Lam EW-F, Mansi J et al. The expression of ERbcx in human breast cancer and the relationship to endocrine therapy and survival. Clin Canc Res 2004; 10: 2421–2428. 22. Macaluso M, Cinti C, Russo G et al. pRb2/p130-E2F4/5-HDAC1-SUV39H1DNMT1 multimolecular complexes mediate the transcription of Estrogen Receptor-a in breast cancer. Oncogene 2003; 22: 3511–3517. 23. Song RX, Santen RJ. Membrane initiated estrogen signaling in breast cancer. Biol Reprod 2006; ?: 000–000. 24. Wallace OB, Lauwers KS, Dodge JA et al. A selective estrogen receptor modulator for the treatment of hot flushes. J Med Chem 2006; 49: 843–846. 25. Nair HB, Luthra R, Kirma N et al. Induction of aromatase expression in cervical carcinomas: effects of endogenous estrogen on cervical cancer cell proliferation. Cancer Res 2005; 65: 11164–11173. 26. Ikeda K, Inoue S. Estrogen receptors and their downstream targets in cancer. Arch Histol Cytol 2004; 67: 435–442.
doi:10.1093/annonc/mdl945 | vii29
Downloaded from http://annonc.oxfordjournals.org/ at Ritsumeikan University on June 6, 2015
1. Deroo BJ, Korach KS. Estrogen receptors and human diseases. J Clin Invest 2006; 116: 561–570. 2. Normanno N, Di Maio M, De Maio E et al. Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer. Endocr-Relat Cancer 2005; 12: 721–747. 3. Reginster JY, Devogelaer JP. Raloxifene reduces fractures in postmenopausal women with osteoporosis. Clin Orthop Relat Res 2006; 443: 48–54. 4. Huang J, Li X, Hilf R et al. Molecular basis of therapeutic strategies for breast cancer. Curr Drug Targets Immune Endocr Metabol Disord 2005; 5: 379–396. 5. Gururaj AE, Rayala SK, Vadlamudi RK et al. Novel mechanisms of resistance to endocrine therapy: genomic and nongenomic considerations. Clin Cancer Res 2006; 12 (3 Pt2): 1001s–1007s. 6. Leclercq G, Lacroix M, Laios I et al. Estrogen receptor alpha: impact of ligands on intracellular shuttling and turnover rate in breast cancer cells. Curr Cancer Drug Targets 2006; 6: 39–64. 7. Houssami N, Cuzick J, Dixon JM. The prevention, detection and management of breast cancer. Med J Aust 2006; 184: 230–234. 8. Lim SC. CD24 and human carcinoma: tumor biological aspects. Biomed Pharmacother 2005; 59 (Suppl 2): S351–354. 9. Saji S, Hirose M, Toi M. Clinical significance of estrogen receptor bin breast cancer. Cancer Chemother Pharmacol 2005; 56 (Suppl 1): s21–s26. 10. Leygue E, Dotzlaw H, Watson PH, Murphy LC. Altered estrogen receptor a and b messenger RNA expression during human breast tumorigenesis. Cancer Res 1998; 58: 3197–3200.
symposium article