AIB1 and its significant role in tumor pathogenesis in systemic malignancies: beyond breast carcinomas

Abstract

Alkner et al. have provided interesting data in their recent article [1.Alkner S. Bendahl P. Grabau D. et al.The role of AIB1 and PAX2 in primary breast cancer: validation of AIB1 as a negative prognostic factor.Ann Oncol. 2013; 24: 1245-1252Abstract Full Text Full Text PDF Scopus (12) Google Scholar]. Amplified in breast cancer 1 (AIB1) may play a major role in tumor growth and progression in a number of other systemic malignancies besides breast carcinomas. A similar association is seen in pulmonary malignancies. Nearly 37.5% of all lung cancers test positive for high levels of AIB1 [2.Wang H. Zhang D. Wu W. et al.Overexpression and gender-specific differences of SRC-3 (SRC-3/AIB1) immunoreactivity in human non-small cell lung cancer: an in vivo study.J Histochem Cytochem. 2010; 58: 1121-1127Crossref PubMed Scopus (20) Google Scholar]. The incidence of overexpression is higher in men in comparison to women. AIB1 overexpression is closely related to tumor cell proliferation. The incidence of AIB1 expression is pretty much the same in lung adenocarcinomas as well as lung squamous cell carcinomas. AIB1 overexpression is thus closely associated with overall poor clinical outcome. AIB1 expression is also closely associated with lymph node staging. Not surprisingly, decreased survival rates are seen in patients with AIB1 overexpression. Similar relationships are seen in prostatic malignancies. Interestingly, a close relationship exists between the risk of developing prostatic malignancy and the CAG/CAA repeat length in the AIB1 gene. In fact, the CAG/CAA repeat length of the AIB1 gene serves as a significant marker of prostate cancer when used in conjunction with the CAG/CAA repeat lengths in the androgen receptor gene [3.Hsing A.W. Chokkalingam A.P. Gao Y.T. et al.Polymorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk: a population-based case–control study.Cancer Epidemiol Biomarkers Prev. 2002; 11: 337-341PubMed Google Scholar]. Downregulation of AIB1 is associated with decreased cdk2 expression. Similar relationships are seen in ovarian malignancies. Increased tumor invasiveness is seen in ovarian carcinomas that overexpress AIB1. Nearly, 65% of all ovarian malignancies express AIB1 [4.Han X.Y. Chen Y. Hou M.M. et al.Expression of AIB1 protein in epithelial ovarian cancer cells and its impact on apoptosis.Sichuan Da Xue Xue Bao Yi Xue Ban. 2008; 39: 619-622, 634PubMed Google Scholar]. Interestingly, increased AIB1 expression is associated with upregulated p53 expression. Overexpression of AIB1 is associated with higher tumor grade as well as stage. Also augmented Bcl-2 expression is typically seen with increased AIB1 expression. More malignant behavior is typically seen in ovarian tumors that express a shorter AIB1 genotype. For instance, the time to disease recurrence in a recent study was 15 months in those with shorter AIB1 genotypes in contrast to 30 months in those with a longer AIB1 genotype [5.Li A.J. Lerner D.L. Gapuzan M.E. et al.AIB1 polymorphisms predict aggressive ovarian cancer phenotype.Cancer Epidemiol Biomarkers Prev. 2005; 14: 2919-2922Crossref PubMed Scopus (27) Google Scholar]. It is obvious from the above examples that AIB1 plays an important role in tumor progression and pathogenesis. Further studies are needed to fully understand its role in other systemic malignancies. The author has declared no conflicts of interest.