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Decreased progesterone binding and attenuated progesterone action in cultured human breast carcinoma cells treated
1Department of Microbiology, University of California, Los Angeles 90024-1489.
Abstract:
Specific progesterone binding by cultured human breast carcinoma T47D, MCF-7, and ZR75-1 cells was decreased 25-40% by epidermal growth factor (EGF), with a 50% effective dose of 0.1 nM EGF. Studies with the soluble and particulate fractions prepared after homogenization of T47D cells grown in glass roller bottles revealed equivalent EGF-induced decreases in progesterone binding to receptors in both fractions. Equilibrium progesterone binding studies with these soluble and particulate fractions revealed that EGF decreased the receptor number, but had no effect on affinity. With cells grown adherent to plastic dishes, EGF treatment induced a greater decrease in binding to receptors recovered in the particulate fraction, than to receptors recovered in the soluble fraction. The decrease in progesterone binding induced by 20 nM EGF was maximal after 2 min of cellular EGF treatment for receptors recovered in the soluble fraction, but was only half-maximal after 15 min for receptors recovered in the particulate fraction. Decreased progesterone binding persisted for at least 8 days in cells cultured with 1 nM EGF. Either insulin or EGF stimulated T47D cell proliferation by two- to threefold with a 50% effective dose of 100 nM for insulin and 0.1 nM for EGF. The progestin, R5020, decreased T47D cell growth by 30% with a 50% effective dose of 1 nM. Either EGF or insulin antagonized the inhibitory effect of R5020 on cell reproduction, but progestins did not antagonize the growth stimulatory response of cells to EGF. Progestins increased the number of EGF receptors within 12 h of their addition to T47D cells, but this response was lost after 6 days. These data show that EGF or progesterone can regulate the receptor number of the other, but for cell reproduction, the effect of EGF is dominant over that of progestins.
Insights
Epidermal growth factor (EGF) significantly reduces progesterone binding in breast cancer cells by decreasing receptor number. EGF
Area of Science:
- Endocrinology
- Cell Biology
- Cancer Research
Background:
- Progesterone receptors are crucial in breast cancer.
- Epidermal growth factor (EGF) influences cell proliferation and signaling pathways.
Purpose of the Study:
- To investigate the effect of EGF on progesterone binding in human breast carcinoma cells.
- To elucidate the interaction between EGF and progesterone signaling in T47D cells.
Main Methods:
- Cultured human breast carcinoma cell lines (T47D, MCF-7, ZR75-1) were treated with EGF.
- Progesterone binding assays were performed on soluble and particulate cell fractions.
- Cell proliferation was measured under various treatment conditions.
Main Results:
- EGF decreased specific progesterone binding by 25-40% in T47D, MCF-7, and ZR75-1 cells.
- EGF reduced the number of progesterone receptors without affecting affinity.
- EGF and insulin stimulated T47D cell proliferation, while progestins inhibited it.
- EGF's effect on cell reproduction was dominant over progestins.
Conclusions:
- EGF significantly downregulates progesterone receptor number in breast cancer cells.
- EGF signaling plays a dominant role in regulating breast cancer cell proliferation compared to progestins.
- These findings highlight complex cross-talk between growth factor and steroid hormone signaling in breast cancer.