The MMTV retrovirus is able to activate cellular oncogenes (int genes) by insertion in the vicinity of these genes. This insertion is one of the key events leading to transformation of mammary epithelial cells. The level of int-2 expression is refractory to hormonal stimulation and is highly expressed in cells where MMTV expression is also strong. Moreover, proviral MMTV expression has a clear component of tissue specificity, being mainly expressed in the mammary gland. These observations suggest that a relationship may exist between these two phenomena. After proviral insertion, available evidence argues that an upstream region of the MMTV LTR is able to bind a nuclear factor. This upstream region displays cell-specific activity, which is required for efficient MMTV transcription only in mammary cell lines. Cooperation between the hormonally regulated MMTV promoter and a second transcriptional element is involved in efficient expression from the MMTV promoter, while hormone-independent activation of the proto-oncogene may require only the upstream element.
