title: Down-regulation of tripartite-motif containing 22 expression in breast cancer is associated with a lack of p53-mediated induction.
abstract: Tripartite-motif containing 22 (TRIM22) is a direct p53 target gene and inhibits the clonogenic growth of leukemic cells. Its expression in Wilms tumors is negatively associated with disease relapse. This study addresses if TRIM22 expression is de-regulated in breast carcinoma. Western blotting analysis of a panel of 10 breast cancer cell lines and 3 non-malignant mammary epithelial cell lines with a well-characterized TRIM22 monoclonal antibody showed that TRIM22 protein is greatly under-expressed in breast cancer cells as compared to non-malignant cell lines. Similarly, TRIM22 protein is significantly down-regulated in breast tumors as compared to matched normal breast tissues. Study of cell lines with methylation inhibitor and bisulfite sequencing indicates that TRIM22 promoter hypermethylation may not be the cause for TRIM22 under-expression in breast cancer. Instead, we found that TRIM22 protein level correlates strongly (R=0.79) with p53 protein level in normal breast tissue, but this correlation is markedly impaired (R=0.48) in breast cancer tissue, suggesting that there is some defects in p53 regulation of TRIM22 gene in breast cancer. This notion is supported by cell line studies, which showed that TRIM22 was no longer inducible by p53-activating genotoxic drugs in breast cancer cell lines and in a p53 null cell line H1299 transfected with wild type p53. In conclusion, this study shows that TRIM22 is greatly under-expressed in breast cancer. p53 dysfunction may be one of the mechanisms for TRIM22 down-regulation.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Gay Hui
authors.initials: GH
authors.lastname: Ho
authors.forename: Heng Nung
authors.initials: HN
authors.lastname: Koong
authors.forename: Gayathri
authors.initials: G
authors.lastname: Sivaramakrishnan
authors.forename: Wei Tzer
authors.initials: WT
authors.lastname: Ang
authors.forename: Qiu Mei
authors.initials: QM
authors.lastname: Koh
authors.forename: Valerie C-L
authors.initials: VC
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics*; D002166:Camptothecin / Q000494:pharmacology; D004249:DNA Damage; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D015778:Minor Histocompatibility Antigens; D017239:Paclitaxel / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology; D000070584:Tripartite Motif Proteins; D050257:Tubulin Modulators / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D059004:Topoisomerase I Inhibitors; D000070584:Tripartite Motif Proteins; D050257:Tubulin Modulators; D016159:Tumor Suppressor Protein p53; D001374:Azacitidine; D017239:Paclitaxel; D002166:Camptothecin
keywords: Breast cancer; DNA methylation; TRIM22; p53 Dysfunction