In an accompanying report (Moreno-Cuevas, J. E.; Sirbasku, D. A., In Vitro Cell. Dev. Biol.; 2000), we demonstrated 80-fold estrogen mitogenic effects with MTW9/PL2 rat mammary tumor cells in cultures supplemented with charcoal-dextran-treated serum. All sera tested contained an estrogen reversible inhibitor(s). The purpose of this report is to extend those observations to additional sex steroid-responsive human and rodent cell lines. Every line tested showed a biphasic response to hormone-depleted serum. Concentrations of ≤10% (v/v) promoted substantive growth. At higher concentrations, serum was progressively inhibitory. With estrogen receptor-positive (ER+) human breast cancer cells, rat pituitary tumor cells, and Syrian hamster kidney tumor cells, 50% (v/v) serum caused significant inhibition, which was reversed by very low physiologic concentrations of estrogens. This same pattern was observed with the steroid hormone-responsive LNCaP human prostatic carcinoma cells. Because steroid hormone mitogenic effects are now easily demonstrable using our new methods, the identification of positive results has nullified our original endocrine estromedin hypothesis. We also evaluated autocrine/paracrine growth factor models of estrogen-responsive growth. We asked if insulin-like growth factors I and II, insulin, transforming growth factor alpha, or epidermal growth factor substituted for the positive effects of estrogens. Growth factors did not reverse the serum-caused inhibition. We asked also if transforming growth factor beta (TGFβ) substituted for the serum-borne inhibitor. TGFβ did not substitute. Altogether, our results are most consistent with the concept of a unique serum-borne inhibitor as has been proposed in the estrocolyone model. However, the aspect of the estrocolyone model related to steroid hormone mechanism of action requires more evaluation. The effects of sex steroids at picomolar concentrations may reflect mediation via inhibitor 'activated' intracellular signaling pathways.
|Number of pages||19|
|Journal||In Vitro Cellular and Developmental Biology - Animal|
|Publication status||Published - 1 Jan 2000|
Bibliographical noteFunding Information:
We gratefully acknowledge the expert technical assistance of Ms. Tameka S. Smith, Mrs. Frances E. Leland, and Mrs. Lyudmila Zilberman. We also thank Ms. Emily Ballou for conducting human breast cancer cell growth assays. This research was supported by grants DAMD17-94-J-4473, DAMD17-98-1-8337, and DAMD17-99-1-9405 from the Department of Defense, U.S. Army Medical Research and Material Command, Breast Cancer Research Program, grants-in-aid from the Women's Fund for Health Education Research, Houston, Texas, a grant-in-aid from the Houston Texas Chapter of the Susan G. Komen Breast Cancer Foundation, and a grant-in-aid from the Cancer Federation, Banning, California.
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All Science Journal Classification (ASJC) codes
- Developmental Biology
- Cell Biology