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Department of Physiology and Biophysics, University of Illinois and University of Illinois College of Medicine, Urbana, Illinois 61801 [L. D. R., B. S. K.], and Division of Hematology and Oncology, University of California Medical School, Los Angeles, California 90024 [D. K., D. J. S.]
Recent work has suggested that overexpression of the HER-2/neu protooncogene may play a role in the aggressive clinical behavior of some breast tumors. Since hormones are also known to change the proliferation rate and invasiveness of these cells, we have studied the effect of sex steroid hormones and antihormones on levels of the HER-2/neu mRNA and protein in human breast cancer cell lines using complementary DNA and antibody probes. In MCF-7 cells, which contain high levels of estrogen receptor and an estradiol (E2)-inducible progesterone receptor (PR), 1 nM E2 caused a rapid drop in HEr-2/neu mRNA (4.8 kilobases), to 40% of control values by 6 h, and a more gradual decrease in HER-2/neu protein, to 50% by 24 h. HER-2/neu protein and mRNA levels remained reduced throughout 1 week of E2 treatment. The effect of E2 was dose dependent, with the maximal effect seen with concentrations of 10–10 M E2 and above, and antiestrogen partly reversed the E2-induced decrease in HER-2/neu expression. These characteristics suggest that the observed modulation of HEr-2/neu is an estrogen receptor-mediated process. In contrast, progestins did not change HER-2/neu mRNA or protein levels in E2-primed MCF-7 cells that contain high levels of PR; in T47D cells, which contain low levels of ER and high levels of PR, addition of E2 or the progestin R5020 or the antiprogestin RU38,486 had no significant effect on HER-2/neu mRNA or protein levels over 6 days of treatment. These results indicate that estrogen but not progestin modulates HER-2/neu protooncogene expression in these breast cancer cell lines and suggest that aggressiveness associated with high levels of HER-2/neu mRNA and protein may be uncoupled from estrogen-stimulated proliferation in these cells.
1 Supported by NIH grants CA18119 and CA51482 and American Cancer Society grant PDT-370 (B. S. K) and by NIH grant CA36827 and American Cancer Society Faculty Research Award (D. J. S). Part of this work was presented at the 80th Annual Meeting of the American Association for Cancer Research, May 1989 (54).
2 To whom requests for reprints should be addressed, at Department of Physiology and Biophysics, University of Illinois, 524 Burrill Hall, 407 S. Goodwin Avenue, Urbana, IL 61801.
Received 7/20/89.
Revised 1/29/90.
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