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Growth of mammary epithelial cells in breast cancer biopsies correlates with EGF binding
158s
D-049 GROWTH
OF
~~A~~~ARY
EPITHELIAL
CELLS
IN
BREAST
CANCER
BIOPSIES
CORRELATES
WITH EGF BINDING
R. Central Institute of Molecular Spitzer, E., Kunde, 0. and Grosse, Biology and Central Institute of Cancer Research of the Academy of Sciences of the GDR, Berlin, GDR. In order to understand the role of EGF,@r the development of human mammary epithelial tissue the binding of J-EGF to cryg24at sections J-EGF binding of breast cancer biopsies was analysed. A mean specific of 8.9 fmol per mg protein was estimated in Tl&% of the investigated Microautoradiagraphic analysis of J-EGF binding to the biopsies. tissue sections was applied to demonstrate that EGF was bound predominantly to mammary epithelial cells. The binding was clearly correlated to the number of mitoses of mammary epithelial cells in the same samples. Significant higher EGF binding values were found in biopsies from breast from cancer cancer with local lymph node metastases, compared to biopsies without lymph node incidence.
D-050
INTERACTIONS BETWEEN OESTROGEN, PROGESTOGEN AND CYTOTOXIC DRUGS IN HUMAN BREAST CANCER CELLS IN CULTURE. *Shaikh N., McNeil1 JM., Pate1 K., *Ghilchik M. and Braunsberg H. Department of Chemical Pathology and *The Breast Clinic, St. Mary's Hospital Medical School, London W2 1PG. A chemotherapeutic regimen involving three cycles of pretreatment with oestrogen (1 wk) and progestogen (2 wk) followed by alternate cytotoxic drug combinations has given remarkable effects in 36 of 40 patients with advanced breast cancer. The present work was undertaken to elucidate hormone and drug interactions. Cultured MCF-7 cells were used as a model for these studies. In the presence of phenol red (pr) which, like oestradiol IE2) increases cell numbers, methotrexate (MTX) and vincristine (VCR) were more effective than in its absence. At a concentration which did not decrease cell numbers, VCR enhanced the effect of MTX on cells exposed to a steroid- and pr-free medium for 3d prior to 24-hr drug exposure. In the absence of steroids and pr medroxyprogesterone acetate (MPA) at 1OnM fails to inhibit and can increase proliferation while E2 increases cell numbers at IpM with a maximal effect at 1OpM. Exposure to E2 (24 hrl or to MPA (48 hr) had little effect on cell numbers. Pretreatment with E2 but not MPA potentiated the effect of MTX but not VCR. Progestogen and cytotoxic drugs may act on different cell populations to produce additive effects. Oestrogen may enhance the effects of some cytotoxic drugs as well as those of progestogen. Such interactions could explain the high efficacy of this regimen. Further therapeutic advantage nay be gained by exploiting positive interactions between cytotoxic drugs in human breast cancer cells.
D-051
EFFECTS OF HORMONES ON CULTURED HUMAN BREAST CANCER CELLS UNDER CONDITIONS OF LOW MITOGENIC STIMULATION. Braunsberg H., Coldham N.G. and Pate1 K. Department of Chemical Pathology, St. Mary's dospital Medical School, London W2 IPG. The development of human cancer cell sublines resistant to growth inhibition by medroxyprogesterone acetate (MPA) or pharmacologicallevels of oestradiol (E2) and the demonstration of a proliferative action of phenol red (prl present in media have prompted this reinvestigationof the actions of tamoxifen (TAM), MPA and E2. In the presence of pr, MCF-7 cells responded to TAM (lOOriM),MPA (1nM) and E2 (5pM) with decreased proliferation. Mitogenic effects of E2 were significant at IOpM. A subline resistant to growth inhibition by MPA responded to TAM and high dose E2 with decreases in cell numbers. In the absence of pr, TAM (2@%, MPA (lOnMf and E2 (5pMLM) did not inhibit proliferation of "wild type" MCF-7 cells. Mitogenic effects of E2 were significant at lpM and maximal at IOpM. At pharmacological concentrations, TAM, MPA and E2 inhibit growth by independent mechanisms, and appear to act on stimulated but not "basal growth. Our findings support the reinstatement of oestroaen treatment in the manamement of breast cancer. In vivo, some steroid receptor-positivetumour cells nay similarly proliferate in the absence of significant amounts of endogenous oestrogen and fail to respond to all hormone therapy. Estimates of tumour oestrogen levels may identify such tumours.
D-049 GROWTH
OF
~~A~~~ARY
EPITHELIAL
CELLS
IN
BREAST
CANCER
BIOPSIES
CORRELATES
WITH EGF BINDING
R. Central Institute of Molecular Spitzer, E., Kunde, 0. and Grosse, Biology and Central Institute of Cancer Research of the Academy of Sciences of the GDR, Berlin, GDR. In order to understand the role of EGF,@r the development of human mammary epithelial tissue the binding of J-EGF to cryg24at sections J-EGF binding of breast cancer biopsies was analysed. A mean specific of 8.9 fmol per mg protein was estimated in Tl&% of the investigated Microautoradiagraphic analysis of J-EGF binding to the biopsies. tissue sections was applied to demonstrate that EGF was bound predominantly to mammary epithelial cells. The binding was clearly correlated to the number of mitoses of mammary epithelial cells in the same samples. Significant higher EGF binding values were found in biopsies from breast from cancer cancer with local lymph node metastases, compared to biopsies without lymph node incidence.
D-050
INTERACTIONS BETWEEN OESTROGEN, PROGESTOGEN AND CYTOTOXIC DRUGS IN HUMAN BREAST CANCER CELLS IN CULTURE. *Shaikh N., McNeil1 JM., Pate1 K., *Ghilchik M. and Braunsberg H. Department of Chemical Pathology and *The Breast Clinic, St. Mary's Hospital Medical School, London W2 1PG. A chemotherapeutic regimen involving three cycles of pretreatment with oestrogen (1 wk) and progestogen (2 wk) followed by alternate cytotoxic drug combinations has given remarkable effects in 36 of 40 patients with advanced breast cancer. The present work was undertaken to elucidate hormone and drug interactions. Cultured MCF-7 cells were used as a model for these studies. In the presence of phenol red (pr) which, like oestradiol IE2) increases cell numbers, methotrexate (MTX) and vincristine (VCR) were more effective than in its absence. At a concentration which did not decrease cell numbers, VCR enhanced the effect of MTX on cells exposed to a steroid- and pr-free medium for 3d prior to 24-hr drug exposure. In the absence of steroids and pr medroxyprogesterone acetate (MPA) at 1OnM fails to inhibit and can increase proliferation while E2 increases cell numbers at IpM with a maximal effect at 1OpM. Exposure to E2 (24 hrl or to MPA (48 hr) had little effect on cell numbers. Pretreatment with E2 but not MPA potentiated the effect of MTX but not VCR. Progestogen and cytotoxic drugs may act on different cell populations to produce additive effects. Oestrogen may enhance the effects of some cytotoxic drugs as well as those of progestogen. Such interactions could explain the high efficacy of this regimen. Further therapeutic advantage nay be gained by exploiting positive interactions between cytotoxic drugs in human breast cancer cells.
D-051
EFFECTS OF HORMONES ON CULTURED HUMAN BREAST CANCER CELLS UNDER CONDITIONS OF LOW MITOGENIC STIMULATION. Braunsberg H., Coldham N.G. and Pate1 K. Department of Chemical Pathology, St. Mary's dospital Medical School, London W2 IPG. The development of human cancer cell sublines resistant to growth inhibition by medroxyprogesterone acetate (MPA) or pharmacologicallevels of oestradiol (E2) and the demonstration of a proliferative action of phenol red (prl present in media have prompted this reinvestigationof the actions of tamoxifen (TAM), MPA and E2. In the presence of pr, MCF-7 cells responded to TAM (lOOriM),MPA (1nM) and E2 (5pM) with decreased proliferation. Mitogenic effects of E2 were significant at IOpM. A subline resistant to growth inhibition by MPA responded to TAM and high dose E2 with decreases in cell numbers. In the absence of pr, TAM (2@%, MPA (lOnMf and E2 (5pMLM) did not inhibit proliferation of "wild type" MCF-7 cells. Mitogenic effects of E2 were significant at lpM and maximal at IOpM. At pharmacological concentrations, TAM, MPA and E2 inhibit growth by independent mechanisms, and appear to act on stimulated but not "basal growth. Our findings support the reinstatement of oestroaen treatment in the manamement of breast cancer. In vivo, some steroid receptor-positivetumour cells nay similarly proliferate in the absence of significant amounts of endogenous oestrogen and fail to respond to all hormone therapy. Estimates of tumour oestrogen levels may identify such tumours.