Zhou Z, Wang J, Han X, Zhou J, Linder S
Department of Oncology-Pathology, Karolinska Hospital, Stockholm, Sweden.
Int J Cancer. 1998 Sep 25;78(1):95-9. doi: 10.1002/(sici)1097-0215(19980925)78:1<95::aid-ijc15>3.0.co;2-4.
In the screening of apoptosis-related genes, an elevated 4.5-kb transcript representing the full-length cDNA of human secreted frizzled-related protein (hsFRP) was cloned. To investigate its possible role in the regulation of cell proliferation, gene expression of hsFRP was examined in human immortalized breast epithelial cell line HBL-100 during growth arrest and apoptosis. Serum deprivation caused G arrest and induction of hsFRP. When serum was re-introduced into the cell culture, the expression of hsFRP declined. Adriamycin treatment induced accumulation of hsFRP mRNA and decrease of beta-catenin. This indicates that the regulation of hsFRP may be involved in the cell-cycle/apoptosis mechanism and possibly in the wnt signaling pathway. hsFRP transcripts were undetectable in cells derived from malignant breast carcinomas, but detectable in 3 immortalized non-malignant breast epithelial cell lines, indicating the involvement of hsFRP in the breast malignant transformation. When tumor and adjacent normal tissues from the same patients were examined, lower expression was found in 5/5 of breast tumors, 2/4 of ovary tumors and 3/5 of kidney tumors. These data suggest the possible involvement of hsFRP in regulation of cell proliferation and breast tumorigenesis.
在凋亡相关基因的筛选过程中，克隆出了一个升高的4.5kb转录本，它代表人类分泌型卷曲相关蛋白（hsFRP）的全长cDNA。为了研究其在细胞增殖调控中的可能作用，在生长停滞和凋亡期间，对人永生化乳腺上皮细胞系HBL-100中的hsFRP基因表达进行了检测。血清剥夺导致G期停滞并诱导hsFRP表达。当将血清重新引入细胞培养物中时，hsFRP的表达下降。阿霉素处理诱导了hsFRP mRNA的积累并降低了β-连环蛋白水平。这表明hsFRP的调控可能参与细胞周期/凋亡机制，并且可能参与Wnt信号通路。在源自乳腺恶性肿瘤的细胞中未检测到hsFRP转录本，但在3种永生化非恶性乳腺上皮细胞系中可检测到，这表明hsFRP参与乳腺恶性转化。当检测同一患者的肿瘤组织和相邻正常组织时，发现5/5的乳腺肿瘤、2/4的卵巢肿瘤和3/5的肾肿瘤中hsFRP表达较低。这些数据表明hsFRP可能参与细胞增殖调控和乳腺肿瘤发生。
