title: Mechanism of β-catenin-mediated transcriptional regulation of epidermal growth factor receptor expression in glycogen synthase kinase 3 β-inactivated prostate cancer cells.
abstract: Wnt/β-catenin and EGFR pathways are important in cancer development and often aberrantly activated in human cancer. However, it is very important to understand the mechanism responsible for this activation and the relation between them. Here, we report the mechanism of EGFR expression by transcriptionally active β-catenin in GSK3β-inactivated prostate cancer cells that eventually leads to its enhanced proliferation and survival. Expressions of β-catenin and EGFR are elevated in various cancers specifically in prostate cancer cells, DU145. When GSK3β is inactivated in these cells, β-catenin gets stabilized, phosphorylated at Ser-552 by protein kinase A, accumulates in the nucleus, and regulates the expression of its target genes that include EGFR. Chromatin immunoprecipitation (ChIP) and promoter analysis revealed that the EGFR promoter gets occupied by transcriptionally active β-catenin when elevated in GSK3β-inactivated cells. This phenomenon not only leads to increased expression of EGFR but also initiates the activation of its downstream molecules such as ERK1/2 and Stat3, ultimately resulting in up-regulation of multiple genes involved in cell proliferation and survival.
authors.affiliation: Signal Transduction in Cancer and Stem Cells Laboratory, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
authors.forename: Kiran Kumar Naidu
authors.initials: KK
authors.lastname: Guturi
authors.forename: Tapashi
authors.initials: T
authors.lastname: Mandal
authors.forename: Anirban
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Moumita
authors.initials: M
authors.lastname: Sarkar
authors.forename: Seemana
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Uttara
authors.initials: U
authors.lastname: Chatterjee
authors.forename: Mrinal K
authors.initials: MK
authors.lastname: Ghosh
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020239:Receptor Cross-Talk; D014158:Transcription, Genetic / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology*
chemical_list: D051176:beta Catenin; D066246:ErbB Receptors; D038362:Glycogen Synthase Kinase 3