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dc.contributor.authorSalah, Zaidoun
dc.contributor.authorUziely, Beatrice
dc.contributor.authorJaber, Mohammad
dc.contributor.authorMaoz, Miriam
dc.contributor.authorCohen, Irit
dc.contributor.authorHamburger, Tamar
dc.contributor.authorMaly, Bella
dc.contributor.authorPeretz, Tamar
dc.contributor.authorBar-Shavit, Rachel
dc.date.accessioned2018-09-08T13:50:26Z
dc.date.available2018-09-08T13:50:26Z
dc.date.issued2012-01-30
dc.identifier.issn1530-6860
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/864
dc.description.abstractA pivotal role is attributed to the estrogenreceptor (ER) pathway in mediating the effect of estrogen in breast cancer progression. Yet the precise mechanisms of cancer development by estrogen remain poorly understood. Advancing tumor categorization a step forward, and identifying cellular gene fingerprints to accompany histopathological assessment may provide targets for therapy as well as vehicles for evaluating the response to treatment. We report here that in breast carcinoma, estrogen may induce tumor development by eliciting protease-activated receptor-1 (PAR1) gene expression. Induction of PAR1 was shown by electrophoretic mobility shift assay, luciferase reporter gene driven by the hPar1 promoter, and chromatin-immunoprecipitation analyses. Functional estrogen regulation of hPar1 in breast cancer was demonstrated by an endothelial tube-forming network. Notably, tissue-microarray analyses from an established cohort of women diagnosed with invasive breast carcinoma exhibited a significantly shorter disease-free (P 0.006) and overall (P 0.02) survival of patients that were positive for ER and PAR1, compared to ER-positive but PAR1-negative patients. We propose that estrogen transcriptionally regulates hPar1, culminating in an aggressive gene imprint in breast cancer. While ER patients are traditionally treated with hormone therapy, the presence of PAR1 identifies a group of patients that requires additional treatment, such as anti-PAR1 biological vehicles or chemotherapy.—Salah, Z., Uziely, B., Jaber, M., Maoz, M., Cohen, I., Hamburger, T., Maly, B., Peretz, T., B.-S, R. Regulation of human protease-activated receptor 1 (hPar1) gene expression in breast cancer by estrogen.en_US
dc.language.isoen_USen_US
dc.publisherFederation of American Societies for Experimental Biologyen_US
dc.subjectthrombinen_US
dc.subjecttumoren_US
dc.subjectEREen_US
dc.subjecttissue microarrayen_US
dc.titleRegulation of human protease-activated receptor 1 (hPar1) gene expression in breast cancer by estrogenen_US
dc.typeArticleen_US


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