WISP-2 gene in human breast cancer: Estrogen and progesterone inducible expression and regulation of tumor cell proliferation
WISP-2 gene in human breast cancer: Estrogen and progesterone inducible expression and regulation of tumor cell proliferation
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DOI：
10.1016/s1476-5586(03)80018-0
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发表时间：
2003-01-01
期刊：
影响因子：
4.8
通讯作者：
Banerjee, SK
中科院分区：
文献类型：
--
作者：
Banerjee, S;Saxena, N;Banerjee, SK
WISP-2 mRNA和蛋白在乳腺癌前病变和癌细胞中均呈高表达。统计分析显示WISP-2表达与雌激素受体（ER）阳性之间存在显著相关性。在正常乳腺中，该表达几乎未被检测到。研究表明，WISP-2是雌激素诱导的MCF-7细胞早期反应基因，其表达持续增加，24 h达到最高水平。纯抗雌激素（ICI 182，780）可抑制雌激素效应。未检测到或最低限度检测到WISP-2表达的人乳腺上皮细胞在用ER-α转染后通过上调WISP-2基因对17 β-雌二醇作出反应，进一步证明WISP-2表达是通过ER-α介导的。雌激素诱导WISP-2 mRNA的过表达可能通过转录激活和稳定两种途径实现。暴露于孕酮的MCF-7细胞WISP-2表达迅速但短暂增加，PR拮抗剂RU 38486阻断了这种mRNA诱导。孕酮与雌二醇联合作用可抑制WISP-2 mRNA的表达。此外，通过使用反义寡聚体破坏MCF-7细胞中的WISP-2信号传导导致肿瘤细胞增殖显著降低。结果与WISP-2表达是乳腺肿瘤细胞增殖的必要条件的结论一致。
WISP-2 mRNA and protein was overexpressed in preneoplastic and cancerous cells of human breast. Statistical analyses show a significant association between WISP-2 expression and estrogen receptor (ER) positivity. In normal breast, the expression was virtually undetected. The studies showed that WISP-2 is an estrogen-induced early response gene in MCF-7 cells and the expression was continuously increased to reach a maximum level at 24 h. The estrogen effect was inhibited by a pure antiestrogen (ICI 182,780). Human mammary epithelial cells, in which WISP-2 expression was undetected or minimally detected, responded to 17beta-estradiol by upregulating the WISP-2 gene after transfection with ER-alpha, providing further evidences that WISP-2 expression is mediated through ER-alpha. Overexpression of WISP-2 mRNA by estrogen may be accomplished by both transcriptional activation and stabilization. MCF-7 cells exposed to progesterone had a rapid but transient increase in WISP-2 expression, and PR antagonist RU38486 blocked this mRNA induction. In combination with estradiol, progesterone acted as an antagonist inhibiting the expression of WISP-2 mRNA. Moreover, disruption of WISP-2 signaling in MCF-7 cells by use of antisense oligomers caused a significant reduction in tumor cell proliferation. The results are consistent with the conclusion that WISP-2 expression is a requirement for breast tumor cells proliferation.