Transforming growth factor-beta represses transcription of the mouse mammary tumour virus DNA in cultured mouse mammary cells.

Increased expression of mouse mammary tumour virus (MMTV) is associated with hyperplastic alveolar growth and subsequent development of mammary cancers in the mouse. The expression of this virus is repressed when mammary tumour cells undergo sarcomatous transformation. We have demonstrated that a spontaneous progression of mouse mammary adenocarcinoma cells into highly malignant cells with the transformed phenotype is accompanied by an increased expression of transforming growth factors alpha and beta (TGF alpha and TGF beta), as well as a decreased expression of MMTV. Mouse mammary adenocarcinoma cells transformed with activated ras oncogene also expressed high levels of the transforming growth factors and a low level of MMTV. Thus a reverse correlation exists between the increased expression of the transforming growth factors and a low level of expression of MMTV. Mouse mammary cells that express high levels of MMTV when treated with exogenous TGF alpha and TGF beta 1 showed a down regulation of MMTV expression in response to TGF beta 1 but not to TGF alpha. These results demonstrate that the repression of MMTV expression in mouse mammary tumour progression may be due in part to an increased expression of TGF beta.