Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Via P. Maroncelli 40, I-47014 Meldola (FC), Italy.
Oncol Rep. 2012 Feb;27(2):403-8. doi: 10.3892/or.2011.1529. Epub 2011 Nov 8.
Deregulation of signal transduction pathways frequently confers selective biological advantages to tumors. Phosphoinositides play an essential role in numerous cellular functions and, among the enzymes implicated in these processes, phosphoinositide-specific phospholipase C β1 (PI-PLCβ1) is one of the key regulators. In the present study, a fluorescence in situ hybridization (FISH) approach was used to investigate PI-PLCβ1 gene copy number alterations in various types of breast cancer differing in their invasiveness and proliferative activity, according to their mitotic index. At the molecular level, we also performed both real-time PCR and immunohistochemical analyses on PI-PLCβ1 to further investigate its expression in primary breast cancers. Finally, we analyzed the correlation between PI-PLCβ1 gene copy number and clinicopathological parameters. Our results show that most of our cases had aneusomies on the PI-PLCβ1 locus (20p12) and amplification of this specific region was the most frequent alteration observed. Our findings also indicate that the amplification of the region containing the PI-PLCβ1 gene was mostly related to the mitotic index, rather than to the invasion status. Finally, even though our case series is limited, PI-PLCβ1 gene amplification seems to be correlated to clinicopathological parameters.
信号转导通路的失调经常赋予肿瘤选择性的生物学优势。磷酸肌醇在许多细胞功能中发挥着重要作用，而在涉及这些过程的酶中，磷酸肌醇特异性磷脂酶 Cβ1（PI-PLCβ1）是关键调节因子之一。在本研究中，根据有丝分裂指数，我们使用荧光原位杂交（FISH）方法研究了不同侵袭性和增殖活性的乳腺癌中 PI-PLCβ1 基因拷贝数的改变。在分子水平上，我们还对 PI-PLCβ1 进行了实时 PCR 和免疫组织化学分析，以进一步研究其在原发性乳腺癌中的表达。最后，我们分析了 PI-PLCβ1 基因拷贝数与临床病理参数之间的相关性。我们的结果表明，我们的大多数病例在 PI-PLCβ1 基因座（20p12）上存在非整倍性，并且该特定区域的扩增是观察到的最常见的改变。我们的研究结果还表明，包含 PI-PLCβ1 基因的区域的扩增主要与有丝分裂指数有关，而与侵袭状态无关。最后，尽管我们的病例系列有限，但 PI-PLCβ1 基因扩增似乎与临床病理参数相关。
