Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2010 Feb 5;392(2):150-4. doi: 10.1016/j.bbrc.2009.12.174. Epub 2010 Jan 6.
PSF3 (partner of Sld five 3) is a member of the tetrameric complex termed GINS, composed of SLD5, PSF1, PSF2, and PSF3, and well-conserved evolutionarily. Previous studies suggested that some GINS complex members are upregulated in cancer, but PSF3 expression in colon carcinoma has not been investigated. Here, we established a mouse anti-PSF3 antibody, and examined PSF3 expression in human colon carcinoma cell lines and colon carcinoma specimens. We found that PSF3 is expressed in the crypt region in normal colonic mucosa and that many PSF3-positive cells co-expressed Ki-67. This suggests that PSF3-positivity of normal mucosa is associated with cell proliferation. Expression of the PSF3 protein was greater in carcinoma compared with the adjacent normal mucosa, and even stronger in high-grade malignancies, suggesting that it may be associated with colon cancer progression. PSF3 gene knock-down in human colon carcinoma cell lines resulted in growth inhibition characterized by delayed S-phase progression. These results suggest that PSF3 is a potential biomarker for diagnosis of progression in colon cancer and could be a new target for cancer therapy.
PSF3(SLD5 的伙伴)是四聚体复合物 GINS 的成员之一,由 SLD5、PSF1、PSF2 和 PSF3 组成,在进化上高度保守。先前的研究表明,一些 GINS 复合物成员在癌症中上调,但结肠癌中 PSF3 的表达尚未被研究过。在这里,我们建立了一种小鼠抗 PSF3 抗体,并检测了人结肠癌细胞系和结肠癌标本中 PSF3 的表达。我们发现 PSF3 在正常结肠黏膜的隐窝区域表达,并且许多 PSF3 阳性细胞共同表达 Ki-67。这表明正常黏膜的 PSF3 阳性与细胞增殖有关。PSF3 蛋白在癌组织中的表达高于相邻正常黏膜,在高级别恶性肿瘤中甚至更强,表明其可能与结肠癌的进展有关。在人结肠癌细胞系中敲低 PSF3 基因导致以 S 期进展延迟为特征的生长抑制。这些结果表明 PSF3 可能是结肠癌进展诊断的潜在生物标志物,也可能是癌症治疗的新靶点。