Glucocorticoid growth suppression response in 13762NF adenocarcinoma-derived Con8 rat mammary tumor cells is mediated by dominant trans-acting factors

Abstract

The in vitro and in vivo growth of Con8 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 (Con8 transfected with the histidinol dehydrogenase selectable marker) and either glucocorticoid-resistant 8RUV7 mammary tumor cells (derived from Con8) or MCT-HTC rat hepatoma cells. Both of the glucocorticoid-resistant 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 glucocorticoid-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 Con8.hD6 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 [3H]thymidine incorporation demonstrated that growth of both the intratissue (Con8.hD6 x 8RUV7) and intertissue (Con8.hD6 x MCT-HTC) 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-suppressible phenotype of Con8 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.