Glucocorticoid Growth Suppression Response in 13762NF Adenocarcinoma-derived ConS Rat Mammary Tumor Cells Is Mediated by Dominant Trans-acting Factors'

The in vitro and in vivo growth of ConS cells, a single cell-derived subclone of the 13762NF-transplantable rat mammary adenocarcinoma, is strongly suppressed by glucocorticoid hormones. Hybrids were formed between glucocorticoid-suppressible Con8.hD6 mammary tumor cells (ConS transfected with the histidinol dehydrogenase selectable marker) and either glucocorticoid-resistant 8RUV7 mammary tumor cells (derived from ConS) or MCT-HTC rat hepatoma cells. Both of the glucocorticoidresistant 8RUV7 and MCT-HTC fusion partners express functional glucocorticoid receptors, since hormone-responsive genes such as plasminogen activator inhibitor are fully dexamethasone inducible. Karyotypic analyses revealed that the hybrid cell populations possessed the appropriate number of chromosomes for a fusion between the glucocor ticoid-suppressible and either of the two resistant cell types. Moreover, Northern blots showed that the intertissue hybrids expressed transcripts for both the milk fat globule membrane protein gene originating from the parental ConS.hDo mammary tumor cells as well as mouse mammary tumor virus glycoprotein sequences which had been transfected into the MCT-HTC hepatoma cells as a molecular tag. Analysis of DNA content and |'H|thymidine incorporation demonstrated that growth of both the intratissue (ConS.hDo x 8RUV7) and intertissue (ConS.hDo x MCTHTC) hybrids was glucocorticoid suppressible, even though the absolute rates of proliferation differed depending on the parental cells. Analysis of conditioned medium isolated from glucocorticoid-treated and untreated Con8.hD6 cells indicated that the growth suppression response is not mediated through the elaboration of an extracellular growth inhibitor. Taken together, our results demonstrate that the glucocorticoid-suppres sible phenotype of ConS rat mammary tumor cells is dominant, suggesting the existence of intracellular regulatory factors under glucocorticoid control that may function as trans-acting suppressors of tumor cell growth.