title: Paired-Box genes are frequently expressed in cancer and often required for cancer cell survival.
abstract: The paired-box (PAX) genes encode a family of nine well-characterized paired-box transcription factors, with important roles in development and disease. Although PAX genes are primarily expressed in the embryo, constitutive expression promotes tissue hyperplasia. Rare tumor-specific mutations of PAX genes implicate an oncogenic role, and persistent PAX expression characterizes several tumors. Yet, a cancer-wide analysis of PAX gene expression to investigate a general role for PAX genes has not been performed. We analysed the pattern and requirement for PAX gene expression in a panel of common cancer cell lines. Very frequent PAX gene expression was identified in tumor cell lines, including lymphoma, breast, ovarian, lung, and colon cancer. In addition, the PAX2 gene was frequently expressed in a panel of 406 common primary tumor tissues. Apoptosis was rapidly induced in ovarian and bladder cancer cell lines following RNA interference to silence PAX2 expression, despite concomitant TP53 and/or HRAS mutations. These data suggest that PAX genes are frequently expressed in cancer, and that endogenous PAX gene expression is required for the growth and survival of cancer cells.
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Muratovska
authors.forename: Chaoming
authors.initials: C
authors.lastname: Zhou
authors.forename: Shuji
authors.initials: S
authors.lastname: He
authors.forename: Paul
authors.initials: P
authors.lastname: Goodyer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Eccles
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D051762:PAX2 Transcription Factor; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D000072636:PAX8 Transcription Factor; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C068686:Pax3 protein, mouse