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Inhibitory Effects of Activin on the Growth and Morphogenesis of Primary and Transformed Mammary Epithelial Cells¹

Departments of Medical Oncology [Q. Y. L., P. G., J. J. G., R. C. C., L. B.] and Biochemistry [Q. Y. L., L. B.], Charing Cross and Westminster Medical School, Fulham Palace Road, London W6 8RF; Division of Cell Biology and Experimental Pathology, Institute of Cancer Research, 15 Cotswald Road, Sutton, Surrey SM2 5NG [B. N.]; and FACS Analysis Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX [D. D.], United Kingdom

Activin is a member of the transforming growth factor ß superfamily, which is known to have activities involved in regulating differentiation and development. By using reverse transcription-PCR analysis on immunoaffinity-purified human breast cells, we have found that activin ßa and activin type II receptor are expressed by myoepithelial cells, whereas no expression was detected in other breast cell types. In examining 15 breast cell lines, we have found only four (HBL-100, MCF10-A, PMC-42, and BT 20) to be positive for activin ßa mRNA, whereas all expressed the activin type II receptor. Furthermore, we have found activin A to be a potent growth inhibitor of MCF-7 cells (at 2 ng/ml), where it causes an arrest in G₁. Activin A does not appear to have an effect on the cell cycle of primary myoepithelial or luminal cells. However, we demonstrate that activin is an inhibitor of tubule formation by human mammary organoids in vitro. These are the first observations of activin and activin receptor in the normal human breast and in human breast cell lines and suggest a role for activin in mammary cell growth and morphogenesis.

¹ This work was supported by grants from the Medical Research Council (United Kingdom), the Special Trustees of Charing Cross and Westminster Medical School, and the Cancer Research Campaign.

² To whom requests for reprints should be addressed.

Received 6/20/95. Accepted 1/ 3/96.

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