Variable responsiveness of hormone-inducible hybrid genes in different cell lines.
Altered steroid responsiveness leads to various pathological conditions and is a particular problem for the treatment of cancers arising in steroid-sensitive cells. To develop cellular model systems for the analysis of the molecular mechanisms mediating altered steroid responses, we have analyzed the inducibility of a steroid-responsive promoter in different cell lines. In vitro constructs containing the mouse mammary tumor virus promoter fused to the herpes simplex virus thymidine kinase gene or the bacterial neo gene were transfected into four different cell lines [Rat-2, CHO chinese hamster ovary cells, F9, and T47D). Thymidine kinase+ clones and neo-resistant clones were selected in the presence of dexamethasone (dex) and/or other steroid hormones. We find that the mouse mammary tumor virus promoter activity is completely dependent on the presence of dex in Rat-2 cells but is constitutively active in CHO cells and is inactive in F9 teratocarcinoma cells in the presence and absence of dex. In the human breast cancer cell line T47D, we observe no response to dex but do observe an inducibility by progesterone. Examination of glucocorticoid receptors in these cell lines showed that Rat-2, CHO, and F9 cells contain sufficient receptors to allow a hormonal response, whereas in T47D cells several glucocorticoid binding activities appear to be present. Our results indicate that the presence of receptor in cells is not always sufficient to allow hormonal activation and that, in some cell lines, like CHO, other factors are present that can substitute for an activated steroid hormone receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)
Wu
K C
KC
Cancer Research Center, La Jolla Cancer Research Foundation, California 92037.
Pfahl
M
M
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D006224:Cricetinae; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone