Lee Won Jae, Roberts-Thomson Sarah J, Monteith Gregory R
The School of Pharmacy, The University of Queensland, Brisbane, Qld 4072, Australia.
Biochem Biophys Res Commun. 2005 Nov 25;337(3):779-83. doi: 10.1016/j.bbrc.2005.09.119. Epub 2005 Sep 28.
There is evidence to suggest that plasma membrane Ca2+-ATPase (PMCA) isoforms are important mediators of mammary gland physiology. PMCA2 in particular is upregulated extensively during lactation. Expression of other isoforms such as PMCA4 may influence mammary gland epithelial cell proliferation and aberrant regulation of PMCA isoform expression may lead or contribute to mammary gland pathophysiology in the form of breast cancers. To explore whether PMCA2 and PMCA4 expression may be deregulated in breast cancer, we compared mRNA expression of these PMCA isoforms in tumorigenic and non-tumorigenic human breast epithelial cell lines using real time RT-PCR. PMCA2 mRNA has a higher level of expression in some breast cancer cell lines and is overexpressed more than 100-fold in ZR-75-1 cells, compared to non-tumorigenic 184B5 cells. Although differences in PMCA4 mRNA levels were observed between breast cell lines, they were not of the magnitude observed for PMCA2. We conclude that PMCA2 mRNA can be highly overexpressed in some breast cancer cells. The significance of PMCA2 overexpression on tumorigenicity and its possible correlation with other properties such as invasiveness requires further study.
有证据表明,质膜Ca2 + -ATP酶(PMCA)亚型是乳腺生理学的重要调节因子。特别是PMCA2在哺乳期会大量上调。其他亚型如PMCA4的表达可能会影响乳腺上皮细胞的增殖,而PMCA亚型表达的异常调节可能会导致乳腺癌形式的乳腺病理生理学或对其产生影响。为了探究PMCA2和PMCA4的表达在乳腺癌中是否失调,我们使用实时RT-PCR比较了这些PMCA亚型在致瘤性和非致瘤性人乳腺上皮细胞系中的mRNA表达。与非致瘤性184B5细胞相比,PMCA2 mRNA在一些乳腺癌细胞系中表达水平更高,并且在ZR-75-1细胞中过表达超过100倍。虽然在乳腺细胞系之间观察到了PMCA4 mRNA水平的差异,但它们的幅度不如PMCA2观察到的那样大。我们得出结论,PMCA2 mRNA在一些乳腺癌细胞中可以高度过表达。PMCA2过表达对致瘤性的意义及其与侵袭性等其他特性的可能相关性需要进一步研究。