- Email: [email protected]
Molecular epidemiology as a power tool for skin cancer screening
Abstracts
E.poster – [A-10-737-2] Mutated p53 binds to estrogen receptor 1 promoter in estrogen negative human breast cancer cells Mozhgan Rasti, Rita Arabsolghar, Zahed Khatooni, Zoherh Mostafavi-Pour Recombinant Protein Lab, Department of Biochemistry, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran E-mail address: [email protected] (M. Rasti) Introduction: P53 is a tumor suppressor protein that regulates estrogen receptor 1 (ESR1) expression. To investigate the mechanism of ESR1 gene regulation by p53, chromatin immunoprecipitation was applied to assess the binding of p53, DNMT1, HDAC1 and MeCP2 to both silenced ESR1 promoter in MDA-MB-468 cells and active ESR1 promoter in MCF-7 breast cancer cells. Methods: The ER-positive MCF-7, ER-negative MDA-MB-468 cells and ER and HER2-positive breast cancer cells were used in this study. The binding of p53, DNMT1, HDAC1 and MeCP2 to ESR1 promoter in MDA-MB-468 cells and MCF-7 breast cancer cells was studied by chromatin immunoprecipitation experiments. Results: The results of chromatin immunoprecipitation experiments showed that p53 protein binds to both unmethylated CpG island of the ESR1 promoter in the ER-positive MCF-7 and the hypermethylated ESR1 promoter in the ER-negative MDA-MB-468 cells. However, repression complex including DNMT1, HDAC1 and MeCP2 is only associated with silenced ESR1 in ER-negative MDAMB-468 human breast cancer cells. In addition, ectopically expressed wild type p53 failed to reactivate the ESR1 gene in these cells. Conclusion: These results suggested that specific p53 mutations may contribute to loss of estrogen receptor α expression in breast tumors and also support the hypothesis that mutant p53 is likely to impact DNA methylation. Keywords: Breast cancer, Estrogen receptor 1, Methylated promoter, p53, Epigenetic doi:10.1016/j.clinbiochem.2011.08.038
E.poster – [A-10-869-1] Molecular epidemiology as a power tool for skin cancer screening Mehdi Mokhtari Department of Epidemiology, Tehran Univercity of Medical Science, Tehran, Iran E-mail address: [email protected] Introduction: Molecular epidemiology, a branch of medical science, focuses on the contribution of potential genetic and environmental risk factors, identified at the molecular level, to the etiology, distribution and prevention of disease within families and across populations. It improves our understanding of the pathogenesis of disease by identifying specific pathways, molecules and genes that influence the risk of developing disease. Skin cancer is the most frequent cancer in the white population worldwide. Incidence of basal cell carcinoma, squamous cell carcinoma and malignant melanoma is still increasing. This trend can be counteracted by means of primary and secondary prevention because the main risk factor for skin cancer – UV-radiation – is known, and, early detected, skin cancer can be cured successfully. For early detection of skin cancer suitable markers have to be used to identify persons at risk. Like other developing countries, Iran placed in epidemiological transition as well. Although, cancer is the third cause of death in Iran, its mortality is increasing during recent decades. Conclusion: Indubitable, advanced molecular epidemiology approach needs to be established in Iranian research centers for exact
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primary screening of exposing risk groups and it must be noticed more than ever because of the mortality nature of cancers specially skin cancer. Keywords: Molecular epidemiology, Skin cancer, Risk factor, UV, Screening, Iran doi:10.1016/j.clinbiochem.2011.08.039
Oral – [A-10-992-1] Glutathione S-transferase mu and theta gene variants in developing colorectal cancer using fluorescence hybridization probes in a group of Iranians Monireh Aghajany-Nasaba, Ahmad Movahediana, Mojtaba Panjehpoura, Siamak Samieeb, Farzaneh Rahimic a Department of Clinical Biochemistry, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran b Food and Drug Laboratory Research Center, Ministry of Health and Medical Education, Tehran, Iran c Taleghani Hospital, Tehran, Iran E-mail addresses: [email protected] (M. Aghajany-Nasab), [email protected] (A. Movahedian), [email protected] (M. Panjehpour), [email protected] (S. Samiee), [email protected] (F. Rahimi) Introduction: Cells possess an array of detoxification enzymes which protects them from xenobiotics and carcinogens. Glutathione Stransferases (GSTs) are an important part of cellular defense mechanisms which encoded by polymorphic genes. Although GSTs occupy a key position in biological process, it is surprising that the GSTT1 and GSTM1are completely deleted in high percentage of human population. The aim of this study was investigate the association among GSTM1, GSTT1 deletion polymorphism and development of CRC in a group of Iranian population. Methods: DNA was extracted from blood of 140 CRC patients and 90 healthy people. GSTT1 and GSTM1 were determined using a real-time PCR and fluorescence resonance energy transfer with a Light-Cycler instrument. Fisher exact test was used to assess differences between the patients and control subjects in the distributions of gender, age. To estimate the relative risk for overall and stratified analyses, odds ratios (OR) with 95% confidence intervals (CI) were computed with logistic regression. Results: No differences in GSTM1, GSTT1 null genotypes frequency were perceived in cases and controls stratified by gender (p value=0.14, p value=0.24, respectively). The risk of colorectal cancer was not associated with GSTT1 null genotype (OR = 1.17; 95%CI: 0.64-2.14).The data suggested a trend of increasing risk for null genotype in patients more than 60 years compared and nbsp;with controls (p value=0.057). GSTM1 null genotype carried an increase risk of developing CRC in patients older than 60 years (OR=2.7; 95% CI: 1.03-7.05). Conclusion: There was increased risk of CRC for individuals with GSTM1 null, especially for people older than 60 years. Keywords: Glutathione Transferase, Gene variant, Colorectal cancer, Real-time PCR doi:10.1016/j.clinbiochem.2011.08.040
Oral – [A-10-1202-1] Biological significance and targeting of HER family members in cancer Helmout Modjtahedi Kingston University London, London, UK E-mail address: [email protected]
E.poster – [A-10-737-2] Mutated p53 binds to estrogen receptor 1 promoter in estrogen negative human breast cancer cells Mozhgan Rasti, Rita Arabsolghar, Zahed Khatooni, Zoherh Mostafavi-Pour Recombinant Protein Lab, Department of Biochemistry, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran E-mail address: [email protected] (M. Rasti) Introduction: P53 is a tumor suppressor protein that regulates estrogen receptor 1 (ESR1) expression. To investigate the mechanism of ESR1 gene regulation by p53, chromatin immunoprecipitation was applied to assess the binding of p53, DNMT1, HDAC1 and MeCP2 to both silenced ESR1 promoter in MDA-MB-468 cells and active ESR1 promoter in MCF-7 breast cancer cells. Methods: The ER-positive MCF-7, ER-negative MDA-MB-468 cells and ER and HER2-positive breast cancer cells were used in this study. The binding of p53, DNMT1, HDAC1 and MeCP2 to ESR1 promoter in MDA-MB-468 cells and MCF-7 breast cancer cells was studied by chromatin immunoprecipitation experiments. Results: The results of chromatin immunoprecipitation experiments showed that p53 protein binds to both unmethylated CpG island of the ESR1 promoter in the ER-positive MCF-7 and the hypermethylated ESR1 promoter in the ER-negative MDA-MB-468 cells. However, repression complex including DNMT1, HDAC1 and MeCP2 is only associated with silenced ESR1 in ER-negative MDAMB-468 human breast cancer cells. In addition, ectopically expressed wild type p53 failed to reactivate the ESR1 gene in these cells. Conclusion: These results suggested that specific p53 mutations may contribute to loss of estrogen receptor α expression in breast tumors and also support the hypothesis that mutant p53 is likely to impact DNA methylation. Keywords: Breast cancer, Estrogen receptor 1, Methylated promoter, p53, Epigenetic doi:10.1016/j.clinbiochem.2011.08.038
E.poster – [A-10-869-1] Molecular epidemiology as a power tool for skin cancer screening Mehdi Mokhtari Department of Epidemiology, Tehran Univercity of Medical Science, Tehran, Iran E-mail address: [email protected] Introduction: Molecular epidemiology, a branch of medical science, focuses on the contribution of potential genetic and environmental risk factors, identified at the molecular level, to the etiology, distribution and prevention of disease within families and across populations. It improves our understanding of the pathogenesis of disease by identifying specific pathways, molecules and genes that influence the risk of developing disease. Skin cancer is the most frequent cancer in the white population worldwide. Incidence of basal cell carcinoma, squamous cell carcinoma and malignant melanoma is still increasing. This trend can be counteracted by means of primary and secondary prevention because the main risk factor for skin cancer – UV-radiation – is known, and, early detected, skin cancer can be cured successfully. For early detection of skin cancer suitable markers have to be used to identify persons at risk. Like other developing countries, Iran placed in epidemiological transition as well. Although, cancer is the third cause of death in Iran, its mortality is increasing during recent decades. Conclusion: Indubitable, advanced molecular epidemiology approach needs to be established in Iranian research centers for exact
S13
primary screening of exposing risk groups and it must be noticed more than ever because of the mortality nature of cancers specially skin cancer. Keywords: Molecular epidemiology, Skin cancer, Risk factor, UV, Screening, Iran doi:10.1016/j.clinbiochem.2011.08.039
Oral – [A-10-992-1] Glutathione S-transferase mu and theta gene variants in developing colorectal cancer using fluorescence hybridization probes in a group of Iranians Monireh Aghajany-Nasaba, Ahmad Movahediana, Mojtaba Panjehpoura, Siamak Samieeb, Farzaneh Rahimic a Department of Clinical Biochemistry, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran b Food and Drug Laboratory Research Center, Ministry of Health and Medical Education, Tehran, Iran c Taleghani Hospital, Tehran, Iran E-mail addresses: [email protected] (M. Aghajany-Nasab), [email protected] (A. Movahedian), [email protected] (M. Panjehpour), [email protected] (S. Samiee), [email protected] (F. Rahimi) Introduction: Cells possess an array of detoxification enzymes which protects them from xenobiotics and carcinogens. Glutathione Stransferases (GSTs) are an important part of cellular defense mechanisms which encoded by polymorphic genes. Although GSTs occupy a key position in biological process, it is surprising that the GSTT1 and GSTM1are completely deleted in high percentage of human population. The aim of this study was investigate the association among GSTM1, GSTT1 deletion polymorphism and development of CRC in a group of Iranian population. Methods: DNA was extracted from blood of 140 CRC patients and 90 healthy people. GSTT1 and GSTM1 were determined using a real-time PCR and fluorescence resonance energy transfer with a Light-Cycler instrument. Fisher exact test was used to assess differences between the patients and control subjects in the distributions of gender, age. To estimate the relative risk for overall and stratified analyses, odds ratios (OR) with 95% confidence intervals (CI) were computed with logistic regression. Results: No differences in GSTM1, GSTT1 null genotypes frequency were perceived in cases and controls stratified by gender (p value=0.14, p value=0.24, respectively). The risk of colorectal cancer was not associated with GSTT1 null genotype (OR = 1.17; 95%CI: 0.64-2.14).The data suggested a trend of increasing risk for null genotype in patients more than 60 years compared and nbsp;with controls (p value=0.057). GSTM1 null genotype carried an increase risk of developing CRC in patients older than 60 years (OR=2.7; 95% CI: 1.03-7.05). Conclusion: There was increased risk of CRC for individuals with GSTM1 null, especially for people older than 60 years. Keywords: Glutathione Transferase, Gene variant, Colorectal cancer, Real-time PCR doi:10.1016/j.clinbiochem.2011.08.040
Oral – [A-10-1202-1] Biological significance and targeting of HER family members in cancer Helmout Modjtahedi Kingston University London, London, UK E-mail address: [email protected]