Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cyclic change of human endometrial cells are controlled by the interaction between hypothalamus, pituitary gland and ovaries, thus making the endometrium proliferate, differentiate, exfoliate and then reproduce. The menstrual cycle is divided into three phases which are called follicle, ovulatory and luteal phase by the morphological change of the ovarium. The endometrial cycle is also classified to proliferative, secretory and menstrual phase. Estradiol (E2) stimulates the proliferation of endometrial cells by the indirect positive mechanism activated by the binding of E2 to E2 receptor. Growth factors (IGF- I, EGF, TGF- alpha etc.) induced by the transcription of the gene promote the proliferation of endometrial cells. Progesterone (P) has antagonistic effects on E2 actions and transform proliferative phase to secretory phase in endometrium. It is suggested that the possible mechanism of carcinogenesis of normal endometrium is the progression of endometrial hyperplasia due to the prolonged and unphysiological exposure to E2. The additional role of oncogenes (fos, fms, myc, myb, erb-B, neu) and growth factors on the mechanism of carcinogenesis of hyperplasia to cancer is very interested.
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PMID:[The physiological function of human endometrium]. 178 83

Increasing evidence suggests molecular interactions between erbB2 and other receptor tyrosine kinases, and estrogenic compounds and their cognate receptors. We have recently reported that downregulation of erbB3 abrogates erbB2-mediated tamoxifen resistance in breast cancer cells. On the basis of these data, we hypothesized that erbB3 may play a major role connecting these two sentinel pathways. Interactions were studied using mammary/breast cancer cell lines from wild-type rat c-neu gene transgenic mice and humans. Estradiol promoted cell proliferation and activated erbB2/neu tyrosine kinase, Akt, and mitogen-activated protein kinase signaling exclusively in mammary and breast epithelial cell lines with coexpression of both erbB2 and erbB3. Estradiol action was independent of the transgene promoter (MMTV-LTR) activity, both in vitro and in vivo, as well as c-neu transgene or endogenous erbB2 gene expression. Estrogen induction of cell growth promotion, erbB2/neu activation, and downstream signaling was abrogated by blockade of estrogen receptor (ER) with the pure ER antagonist ICI 182,780 or knockdown of erbB3 expression via specific siRNA. These data suggest that activation of both ER and erbB2/erbB3 signaling is requisite for estrogen-induced mitogenesis and erbB2/neu tyrosine kinase activation.
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PMID:Estrogenic promotion of ErbB2 tyrosine kinase activity in mammary tumor cells requires activation of ErbB3 signaling. 1986 7