Mammary specific expression of elevated levels of mouse mammary tumor virus (MMTV) contributes to mammary carcinogenesis. Mechanisms which regulate provirus expression have not been completely defined. Using a MMTV-long repeat terminal (MMTV-LRT) directed chloramphenicol-acetyltransferase (CAT) reporter gene system and a human breast cancer cell line T47D, we demonstrate that prolactin (PRL), epidermal growth factor (EGF), or transforming growth factor-α (TGF-α) act on a mammary cell-specific enhancer at the extreme 5' end of the MMTV-LTR involving sequences - 1094 through - 858. PRL and either EGF or TGF-α exert concerted roles in this activation of these sequences. In contrast, using a plasmid construct lacking this mammary cell-specific enhancer, EGF or TGF-α, but not PRL, act synergistically with progesterone to induce CAT activity, indicating that the action of PRL on regulatory elements of the MMTV-LTR is restricted to this mammary cell-specific enhancer involving sequences - 1094 through - 858. A mobility shift assay was used to demonstrate that PRL, EGF or TGF-α induce nuclear factors (MP4, MAF, and MGF) which bind directly to this mammary cell-specific enhancer element.
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