Selcuklu S D, Yakicier M C, Erson A E
Genetics and Biotechnology Lab, Room 1.30, BioSciences Institute, University College Cork, Western Road, Cork, Ireland.
Cancer Genet Cytogenet. 2009 Feb;189(1):15-23. doi: 10.1016/j.cancergencyto.2008.09.009.
Various regions of amplification or loss are observed in breast tumors as a manifestation of genomic instability. To date, numerous oncogenes or tumor suppressors on some of these regions have been characterized. An increasing body of evidence suggests that such regions also harbor microRNA genes with crucial regulatory roles in cellular processes and disease mechanisms, including cancer. Here, we investigated 35 microRNAs localized to common genomic gain and/or loss regions in breast cancers. To examine amplification or loss of these microRNAs as a result of genomic instability, we performed semiquantitative duplex polymerase chain reaction in 20 breast cancer cell lines, 2 immortalized mammary cell lines, and 2 normal DNA controls. A comprehensive DNA fold number change data for 35 microRNA genes on chromosomal gain/loss regions are presented in breast cancer cells. A 23% (8/35) of the investigated microRNAs showed significant fold number increases (greater than fourfold) compared to GAPDH in one or more of the breast cell lines. Although no homozygous deletions were detected, fold number decreases indicating potential loss regions were observed for 26% (9/35) of the investigated microRNAs. Such fold number changes may point out some of these microRNAs as potential targets of the genomic instability regions as oncogene and tumor suppressor candidates.
在乳腺肿瘤中观察到各种扩增或缺失区域,这是基因组不稳定的一种表现。迄今为止,这些区域中的许多致癌基因或肿瘤抑制基因已得到表征。越来越多的证据表明,这些区域还含有在细胞过程和疾病机制(包括癌症)中具有关键调控作用的微小RNA基因。在此,我们研究了定位于乳腺癌常见基因组扩增和/或缺失区域的35种微小RNA。为了检查由于基因组不稳定导致的这些微小RNA的扩增或缺失,我们在20种乳腺癌细胞系、2种永生化乳腺细胞系和2种正常DNA对照中进行了半定量双链聚合酶链反应。给出了乳腺癌细胞中染色体扩增/缺失区域上35个微小RNA基因的全面DNA倍数变化数据。在一种或多种乳腺细胞系中,23%(8/35)的研究微小RNA与甘油醛-3-磷酸脱氢酶(GAPDH)相比显示出显著的倍数增加(大于四倍)。虽然未检测到纯合缺失,但在26%(9/35)的研究微小RNA中观察到表明潜在缺失区域的倍数减少。这种倍数变化可能指出其中一些微小RNA作为基因组不稳定区域的潜在靶点,作为致癌基因和肿瘤抑制基因候选物。