Aberrant expression of cell-cycle regulator cyclin D1 in breast cancer is related to chromosomal genomic instability.
To account for the accumulation of genomic alterations required for tumor progression, it has been suggested that the genomes of cancer cells are unstable and that this instability results from defective mutators (the "mutator phenotype" theory). To examine the hypothesis that abnormal cell-cycle regulators act as the mutators contributing to genomic instability, the present study, based on primary tumor tissues from 71 patients with breast cancer, was performed to determine whether there was an association between aberrant expression of cell-cycle regulators (cyclin A, cyclin D1, cyclin E, RB1, p21, and p27) and chromosomal instability. Comparative genomic hybridization was used to measure chromosomal changes, reflecting genomic instability in individual tumors, whereas immunohistochemistry was used to detect aberrant expression of cell-cycle regulators. Overexpression of cyclin D1 was found to be significantly correlated with increased chromosomal instability (defined as harboring more than 7 chromosomal changes), with 63% of tumors overexpressing and 27% of tumors not overexpressing, with cyclin D1 showing chromosomal instability (P < 0.05). Interestingly, this relationship was independent of cell outgrowth (as detected by the proliferation marker Ki-67) and was particularly significant in tumors not expressing p27 or in tumors with detectable RB1. These results suggest that cyclin D1 plays an alternative role in the regulation of genomic stability.
Lung
Jia-Chyi
JC
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Chu
Jan-Show
JS
Yu
Jyh-Cherng
JC
Yue
Chung-Tai
CT
Lo
Yen-Li
YL
Shen
Chen-Yang
CY
Wu
Cheng-Wen
CW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008875:Middle Aged; D009693:Nucleic Acid Hybridization
D018797:Cell Cycle Proteins; D019938:Cyclin D1