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The Hartwell Laboratory [A. B., N. P. M. S., M. B., A. A. C.], Section of Academic Surgery and Departments of Histopathology [K. M.], Medicine [I. S.], Surgery [A. M.], and Biochemistry [M. D.], The Institute of Cancer Research and Royal Marsden Hospital, Fulham Road, London SW3 6JJ, United Kingdom, and Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892 [K. C. F., L. M. W., M. B. S.]
We have investigated the ability of tamoxifen to regulate members of the transforming growth factor ß (TGF-ß) family in human breast cancers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-ß1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient. The induced TGF-ß is locaized between and around stromal fibroblasts and appears to be derived from these cells. Lower levels of TGF-ß1,-ß2, and -ß3 seen in epithelial cells were not altered by tamoxifen treatment. The increased stromal staining of TGF-ß1 occurred in estrogen receptor-negative as well as estrogen receptor-positive tumors. These results provide in vivo evidence for a novel, estrogen receptor-independent mechanism of action for tamoxifen, involving the stromal induction of a potent growth inhibitor for epithelial cells.
1 To whom requests for reprints should be addressed, at The Hartwell Laboratory, Section of Academic Surgery, Institute of Cancer Research, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom.
Received 5/11/92. Accepted 6/12/92.
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