Regulation of transforming growth factor beta 1 by radiation in cells of two human breast cancer cell lines

We have investigated the mechanisms by which radiation inhibits proliferati on of human breast cancer cells in culture. Radiation, within the dose rang e used for treatment of humans, decreased the rate of proliferation of estr ogen-independent MDA-MB-231 cells more effectively than it did that of estr ogen-dependent MCF-7 cells. The rate of proliferation of MDA-MB-231 cells w as also inhibited to a greater extent than that of MCF-7 cells by purified TGFB1, Using an ELISA specific for activated TGFB1, we found that condition ed medium from irradiated MDA-MB-231 or MCF-7 cells contained twofold more TGFB1 than that from nonirradiated cells. Conditioned medium from irradiate d breast cancer cells, but not from nonirradiated cells, inhibited the grow th of untreated MDA-MB-231 cells. The inhibitory activity was blocked by an anti-TGFB1 neutralizing antibody. Gn approximately twofold increase in the TGFB1 mRNA in irradiated cells compared to controls was found using semiqu antitative reverse-transcriptase PCR, Last, the mRNA for insulin-like growt h factor binding protein 3, a reported target of the cell inhibitory activi ty of TGFB1, was increased threefold upon irradiation. Our results demonstr ate that the TGFB1 is increased after irradiation and that the activation o f the TGFB1 signaling pathway may sensitize cells to the effects of radiati on. (C) 1999 by Radiation Research Society.