DNMT3A and DNMT3B mediate autocrine hGH repression of plakoglobin gene transcription and consequent phenotypic conversion of mammary carcinoma cells
作者： F Shafiei , F Rahnama , L Pawella , M D Mitchell , P D Gluckman
关键词: Cancer research 、 Plakoglobin 、 Autocrine signalling 、 Transcription (biology) 、 Carcinogenesis 、 DNA methylation 、 Small interfering RNA 、 DNMT1 、 Biology 、 Psychological repression
摘要: Directed by microarray analyses, we report that autocrine human growth hormone (hGH) increased the mRNA and protein expression of DNA methyltransferase 1 (DNMT1), DNMT3A DNMT3B in mammary carcinoma cells. Autocrine hGH stimulation was mediated JAK2 Src kinases, treatment cells with DNMT inhibitor, 5'-aza-2'-deoxycytidine (AZA), abrogated hGH-stimulated cellular proliferation, apoptosis anchorage-independent growth. AZA reversed epitheliomesenchymal transition induced hGH, to an epithelioid morphology cell migration stimulated hGH. hypermethylation first exon PLAKOGLOBIN gene ability repress plakoglobin transcription. Small interfering RNA (siRNA)-mediated depletion individual molecules did not release repression promoter activity nor affect migration. However, concomitant siRNA-mediated both subsequent transcription Thus, increases mediate direct its consequent phenotypic conversion therefore, utilizes methylation as a mechanism exert oncogenic effects
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