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.