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  • Title: EGF stimulates Pit-1 independent transcription of the human prolactin pituitary promoter in human breast cancer SK-BR-3 cells through its proximal AP-1 response element.
    Author: Manfroid I, Van de Weerdt C, Baudhuin A, Martial JA, Muller M.
    Journal: Mol Cell Endocrinol; 2005 Jan 14; 229(1-2):127-39. PubMed ID: 15607537.
    Abstract:
    Normal and neoplastic human mammary gland cells are targets for the proliferative action of prolactin. These cells also synthesize prolactin, thereby inducing an autocrine/paracrine proliferative loop. We present the first extensive analysis of the transcriptional regulation of the human prolactin gene (hPRL) in human mammary tumor cells, SK-BR-3. We show that the pituitary promoter is functional in these cells in the absence of the pituitary-specific factor Pit-1. Expression of exogenous Pit-1 or epidermal growth factor (EGF) treatment stimulates the transfected hPRL pituitary promoter and the endogenous hPRL expression. EGF stimulation is mediated by increased synthesis of c-fos and c-jun, resulting in AP-1 binding to the proximal hPRL pituitary promoter. This regulation involves the EGF receptor, possibly ErbB2 that is highly expressed in SK-BR-3 cells, and a PI3K/JNK pathway. The stimulation of hPRL gene transcription by EGF in mammary cells may include hPRL in a complex regulatory network controlling growth of human mammary cells.
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