title: Prognostic significance of TRIM24/TIF-1α gene expression in breast cancer.
abstract: In this study, we have analyzed the expression of TRIM24/TIF-1α, a negative regulator of various transcription factors (including nuclear receptors and p53) at the genomic, mRNA, and protein levels in human breast tumors. In breast cancer biopsy specimens, TRIM24/TIF-1α mRNA levels (assessed by Real-Time Quantitative PCR or microarray expression profiling) were increased as compared to normal breast tissues. At the genomic level, array comparative genomic hybridization analysis showed that the TRIM24/TIF-1α locus (7q34) exhibited both gains and losses that correlated with mRNA levels. By re-analyzing a series of 238 tumors, high levels of TRIM24/TIF-1α mRNA significantly correlated with various markers of poor prognosis (such as the molecular subtype) and were associated with worse overall survival. By using a rabbit polyclonal antibody for immunochemistry, the TRIM24/TIF-1α protein was detected in nuclei of normal luminal epithelial breast cells, but not in myoepithelial cells. Tissue microarray analysis confirmed that its expression was increased in epithelial cells from normal to breast infiltrating duct carcinoma and correlated with worse overall survival. Altogether, this work is the first study that shows that overexpression of the TRIM24/TIF-1α gene in breast cancer is associated with poor prognosis and worse survival, and it suggests that this transcription coregulator may play a role in mammary carcinogenesis and represent a novel prognostic marker.
authors: Institut de Recherche en Cancérologie de Montpellier (IRCM), Montpellier, France; INSERM U896, Montpellier, France.
authors: Monique
authors: M
authors: Chambon
authors: Béatrice
authors: B
authors: Orsetti
authors: Marie-Laurence
authors: ML
authors: Berthe
authors: Caroline
authors: C
authors: Bascoul-Mollevi
authors: Carmen
authors: C
authors: Rodriguez
authors: Vanessa
authors: V
authors: Duong
authors: Michel
authors: M
authors: Gleizes
authors: Sandrine
authors: S
authors: Thénot
authors: Frédéric
authors: F
authors: Bibeau
authors: Charles
authors: C
authors: Theillet
authors: Vincent
authors: V
authors: Cavaillès
mesh_terms: D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping / Q000379:methods; D055028:Comparative Genomic Hybridization; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007120:Immunochemistry / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C555317:TRIM24 protein, human; D014157:Transcription Factors; C093517:transcriptional intermediary factor 1