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Characterization of Estrogen Responsive Transforming Activity in Human Breast Cancer Cell Lines

Medical Breast Cancer Section, Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892

We have characterized the production of transforming growth factor (TGF) activities by five human breast cancer cell lines in culture. The presence of TGF- and -ß activity in medium conditioned by these cells was detected by induction of anchorage-independent colony formation of normal rat kidney cells in soft agar and by epidermal growth factor and TGF-ß receptor competition studies. In MCF-7, an estrogen-receptor positive cell line which requires estrogen for tumorigenesis in vivo, 17_ß-estradiol induced a 2-5-fold increase in a TGF--like activity (apparent molecular weight, 68,000 and 30,000 by column chromatography). An estrogen induction of lower magnitude (1.5–2.5-fold) was also seen in two other estrogen responsive cell lines, ZR-75-B and T47D. TGF-ß was not induced by 17_ß-estradiol in any of the three cell lines and was decreased by up to 50% of control in the MCF-7 and T47D cell lines. TGF-ß was not detectable by radioreceptor assay in the ZR-75-B cell line. Two hormone-independent and highly tumorigenic cell lines were studied. The MDA-MB-231 cell line produced large amounts of both TGF--like (M_r 30,000) and TGF-ß activities. In the HS578T cell line, little TGF- was detectable, while large amounts of TGF-ß were produced. No simple correlations between the tumorigenicity of the cell lines in nude mice and production of either TGF activity could be demonstrated.

¹ Supported by National Research Service Award 1 F32 CA 07697-01.

² To whom requests for reprints should be addressed, at Medicine Branch, National Cancer Institute, Bldg. 10, Room 12N226, Bethesda, MD 20892.

Received 8/15/85. Revised 12/ 2/85. Accepted 12/12/85.