This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ryde, C. M. Articles by Dowsett, M. Search for Related Content PubMed PubMed Citation Articles by Ryde, C. M. Articles by Dowsett, M.

Steroid and Growth Factor Modulation of Aromatase Activity in MCF7 and T47D Breast Carcinoma Cell Lines

Department of Academic Biochemistry, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, United Kingdom

The effect of a number of steroids, growth factors, and peptides on aromatase activity in two estrogen receptor positive breast cancer cell lines (MCF7 and T47D) was investigated. The cells were incubated in Dulbecco's minimum essential medium containing phenol red and 10% fetal calf serum. Pronounced differences in basal aromatase activity and different responses to the addition of experimental agents were found in the two cell lines. Aromatase activity in MCF7 cells was significantly stimulated by phorbol 12,13-diacetate [PDA], dibutyryl cyclic AMP [(Bu)₂cAMP], transforming growth factor , and epidermal growth factor individually and PDA and (Bu)₂cAMP in combination, while it was inhibited by dexamethasone and unaffected by transforming growth factor ß, fibroblast growth factor, platelet-derived growth factor, prolactin, and tamoxifen. Addition of cortisol to MCF7 cells had no effect on aromatase activity at 1 nM, caused suppression of activity at 10 nM and stimulated activity at 100 nM. Aromatase activity in T47D cells was stimulated by transforming growth factor , epidermal growth factor, platelet-derived growth factor, prolactin, dexamethasone, and cortisol individually and PDA and (Bu)₂cAMP in combination. It was unaffected by transforming growth factor ß, PDA, (Bu)₂cAMP, and fibroblast growth factor. These findings suggest that aromatase activity is induced by agents which stimulate cyclic AMP-dependent protein kinases [e.g., (Bu)₂cAMP] and that this effect is potentiated by factors which stimulate protein kinase C [e.g., PDA]. The effect on aromatase activity of growth factors, the actions of which are believed to be mediated by receptors linked to tyrosine kinase activity, is not as clearly defined, with a factor causing stimulation, inhibition, and no change in activity depending on the tissue concerned. Further insight into these differences will require resolution of the molecular mechanisms that mediate the actions of stimulatory and repressive growth factors on aromatase activity of oestrogen-producing cells.

¹ To whom requests for reprints should be addressed.

Received 7/29/91. Accepted 1/ 8/92.

This article has been cited by other articles:

				R. Shibuya, T. Suzuki, Y. Miki, K. Yoshida, T. Moriya, K. Ono, J.-i. Akahira, T. Ishida, H. Hirakawa, D. B Evans, et al. Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast Endocr. Relat. Cancer, March 1, 2008; 15(1): 113 - 124. [Abstract] [Full Text] [PDF]

				Y. Miki, T. Suzuki, C. Tazawa, Y. Yamaguchi, K. Kitada, S. Honma, T. Moriya, H. Hirakawa, D. B. Evans, S.-i. Hayashi, et al. Aromatase Localization in Human Breast Cancer Tissues: Possible Interactions between Intratumoral Stromal and Parenchymal Cells Cancer Res., April 15, 2007; 67(8): 3945 - 3954. [Abstract] [Full Text] [PDF]

				J. Hartman, K. Lindberg, A. Morani, J. Inzunza, A. Strom, and J.-A. Gustafsson Estrogen Receptor {beta} Inhibits Angiogenesis and Growth of T47D Breast Cancer Xenografts Cancer Res., December 1, 2006; 66(23): 11207 - 11213. [Abstract] [Full Text] [PDF]

				M. Lu, D. Chen, Z. Lin, S. Reierstad, A. M. Trauernicht, T. G. Boyer, and S. E. Bulun BRCA1 Negatively Regulates the Cancer-Associated Aromatase Promoters I.3 and II in Breast Adipose Fibroblasts and Malignant Epithelial Cells J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4514 - 4519. [Abstract] [Full Text] [PDF]

				T. Okubo, S. C. Mok, and S. Chen Regulation of Aromatase Expression in Human Ovarian Surface Epithelial Cells J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4889 - 4899. [Abstract] [Full Text]

				R. J. Pauley, S. J. Santner, L. R. Tait, R. K. Bright, and R. J. Santen Regulated CYP19 Aromatase Transcription in Breast Stromal Fibroblasts J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 837 - 846. [Abstract] [Full Text]

				S. J. Santner, R. J. Pauley, L. Tait, J. Kaseta, and R. J. Santen Aromatase Activity and Expression in Breast Cancer and Benign Breast Tissue Stromal Cells J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 200 - 208. [Abstract] [Full Text] [PDF]