title: Aberrant expression of X-linked genes RbAp46, Rsk4, and Cldn2 in breast cancer.
abstract: The consequence of activation status or gain/loss of an X-chromosome in terms of the expression of tumor suppressor genes or oncogenes in breast cancer has not been clearly addressed. In this study, we investigated the activation status of the X-chromosomes in a panel of human breast cancer cell lines, human breast carcinoma, and adjacent mammary tissues and a panel of murine mammary epithelial sublines ranging from low to high invasive potentials. Results show that most human breast cancer cell lines were homozygous, but both benign cell lines were heterozygous for highly polymorphic X-loci (IDS and G6PD). On the other hand, 60% of human breast carcinoma cases were heterozygous for either IDS or G6PD markers. Investigation of the activation status of heterozygous cell lines revealed the presence of only one active X-chromosome, whereas most heterozygous human breast carcinoma cases had two active X-chromosomes. Furthermore, we determined whether or not an additional active X-chromosome affects expression levels of tumor suppressor genes and oncogenes. Reverse transcription-PCR data show high expression of putative tumor suppressor genes Rsk4 and RbAp46 in 47% and 79% of breast carcinoma cases, respectively, whereas Cldn2 was down-regulated in 52% of breast cancer cases compared with normal adjacent tissues. Consistent with mRNA expression, immunostaining for these proteins also showed a similar pattern. In conclusion, our data suggest that high expression of RbAp46 is likely to have a role in the development or progression of human breast cancer. The activation status of the X-chromosome may influence the expression levels of X-linked oncogenes or tumor suppressor genes.
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University, 110 East Warren Avenue, Detroit, MI 48201, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Thakur
authors.forename: Km Wahidur
authors.initials: KW
authors.lastname: Rahman
authors.forename: Jack
authors.initials: J
authors.lastname: Wu
authors.forename: Aliccia
authors.initials: A
authors.lastname: Bollig
authors.forename: Hector
authors.initials: H
authors.lastname: Biliran
authors.forename: Xiukun
authors.initials: X
authors.lastname: Lin
authors.forename: Hind
authors.initials: H
authors.lastname: Nassar
authors.forename: David J
authors.initials: DJ
authors.lastname: Grignon
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Liao
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X / Q000235:genetics*; D057167:Claudins; D004847:Epithelial Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D050172:Genes, X-Linked; D006580:Genetic Carrier Screening; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D056524:Retinoblastoma-Binding Protein 7; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C491875:CLDN2 protein, human; D002352:Carrier Proteins; D057167:Claudins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C490746:RBBP7 protein, human; D012333:RNA, Messenger; D056524:Retinoblastoma-Binding Protein 7; D025521:Tumor Suppressor Proteins; C501305:RPS6KA6 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa