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Epidermal Growth Factor Gene Expression in Human Breast Cancer Cells: Regulation of Expression by Progestins¹

Department of Physiology, University of Manitoba [L. C. M., L. J. M., D. D., R. P. C. S.], Winnipeg, Manitoba, Canada R3E 0W3, and Howard Hughes Medical Institute and the Departments of Biochemistry and Molecular Biology and Medicine [G. I. B.], University of Chicago, Chicago, Illinois 60637

Epidermal growth factor (EGF) is thought to be important in normal mammary development. The presence of EGF receptors in breast cancer cells suggests that it may also have a role in regulating growth of tumors of the human breast. Using a complementary DNA probe for the human EGF precursor we have examined expression of this gene in a series of human breast cancer cells in long term culture. The T-47D cell line demonstrated the highest level of EGF mRNA. EGF expression was not detectable in the MCF-7, BT 20, or HBL 100 cell lines. Surprisingly, in both T-47D and ZR 75 cells, pretreatment with progestins which exert antiproliferative effects under the conditions used increased EGF mRNA levels approximately 6-fold above untreated controls. This effect, demonstrable with as little as 0.1 nM of medroxyprogesterone acetate, was apparent as early as 12 h after addition of progestin and was reversed with the antiprogestin RU 486. Dexamethasone, estradiol, and dihydrotestosterone had no effect on EGF expression in T-47D cells. There was no evidence that the increased levels of EGF mRNA were due to gene amplification. Immunoprecipitation of biosynthetically labeled T-47D conditioned medium with antibodies to human EGF and EGF-precursor revealed the presence of both M_r 40,000 and 18,000 products. Fully processed M_r 6,000 EGF was not detectable in either conditioned medium or cell lysate. These data provide unequivocal evidence for the expression of the EGF gene in some human breast cell lines.

¹ This work was supported by grants from the Medical Research Council, St. Boniface Hospital Research Foundation, Manitoba Health and Research Council and the Faculty of Medicine Fund, University of Manitoba.

² Manitoba Health and Research Council Scholar. Present address: Department of Biochemistry, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E OW3. To whom requests for reprints should be addressed.

³ C. J. Martin Fellow of NHMRC of Australia.

⁴ Medical Research Council Student.

⁵ Medical Research Council Scientist.

Received 10/ 1/87. Revised 1/28/88. Revised 5/12/88. Accepted 5/20/88.

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