MUC1-C oncoprotein induces TCF7L2 transcription factor activation and promotes cyclin D1 expression in human breast cancer cells. Rajabi H et al. MUC1 is a heterodimeric glycoprotein that is overexpressed in breast cancers. The present studies demonstrate that the oncogenic MUC1 C-terminal subunit (MUC1-C) associates with the TCF7L2 transcription factor. The MUC1-C cytoplasmic domain (MUC1-CD) binds directly to the TCF7L2 C-terminal region. MUC1-C blocks the interaction between TCF7L2 and the C-terminal-binding protein (CtBP), a suppressor of TCF7L2-mediated transcription. TCF7L2 and MUC1-C form a complex on the cyclin D1 gene promoter and MUC1-C promotes TCF7L2-mediated transcription by the recruitment of -catenin and p300. Silencing MUC1-C in human breast cancer cells down-regulated activation of the cyclin D1 promoter and decreased cyclin D1 expression. In addition, a MUC1-C inhibitor blocked the interaction with TCF7L2 and suppressed cyclin D1 levels. These findings indicate that the MUC1-C oncoprotein contributes to TCF7L2 activation and thereby promotes cyclin D1 expression in breast cancer cells.
NCBI Summary:
This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]
General function
Intracellular signaling cascade
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Cellular localization
Extracellular Matrix, Secreted, Cytoplasmic
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MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. Margarit L et al. (2010) Endometrium of fertile women expresses progesterone-regulated Mucin 1 (MUC1) that carries selectin ligands recognized by the human blastocyst. Altered MUC1 expression at the time of implantation may contribute to endometrial infertility. The aim was to assess the expression of MUC1 in the endometrium from polycystic ovary syndrome (PCOS), endometriosis, and fertile women in comparison with other hormone-regulated proteins [hydroxysteroid dehydrogenase (HSD) 1, HSD2, estrogen receptor (ER) and progesterone receptor (PR)]. Endometrial samples were obtained from 33 fertile patients, 26 ovulatory PCOS patients, 15 anovulatory PCOS patients, and 25 endometriosis patients. Immunohistochemistry assessed the expression of MUC1 subunits ER, PR, HSD1, and HSD2 in endometrial epithelium. Endometrial MUC1 expression was quantified by immunoblots and RT-PCR. HSD1 and HSD2 expression was assayed by RT-PCR. MUC1ND expression was significantly higher in ovulatory PCOS than in fertile and anovulatory PCOS patients, even after progesterone stimulation. MUC1ND and -CD expression was lower in anovulatory PCOS than in fertile patients. Only MUC1CD expression was lower in endometriosis patients. Endometrial ER expression was significantly higher in PCOS and endometriosis patients, whereas PR expression was significantly higher in PCOS than in fertile patients. The expression of HSD1 was significantly higher in anovulatory PCOS than in fertile patients. Expression of HSD2 was significantly higher in PCOS patients and lower in endometriosis patients. Expression of MUC1 subunits in the infertile endometrium is significantly different from fertile and appears to be a component of altered gene expression that potentially contributes to endometrial insufficiency.//////////////////
Ovarian function
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Expression regulated by
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Ovarian localization
Ovarian tumor
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Determination of MUC1 in Sera of Ovarian Cancer Patients and in Sera of Patients with Benign Changes of the Ovaries with CA15-3, CA27.29, and PankoMab. Jeschke U et al. Aim: Mucin 1 (MUC1) is a high molecular weight transmembrane glycoprotein with unique properties which is used as a tumour marker in sera of ovarian cancer patients. The common test kit for the cancer antigen 15-3 (CA15-3) is not sufficient for the discrimination between sera from healthy individuals and sera from patients with benign changes of the ovaries. In this study, the newly developed anti-MUC1 antibody PankoMab was tested in normal and patient sera with an ELISA, and the obtained data were compared against data from experiments using the commercial kits for CA15-3 and CA27.29.