Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer
Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer
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DOI：
10.1007/s10549-011-1883-6
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发表时间：
2012-06-01
影响因子：
3.8
通讯作者：
Lamb, Caroline A.
中科院分区：
文献类型：
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作者：
Cerliani, Juan P.;Vanzulli, Silvia I.;Lamb, Caroline A.
成纤维细胞生长因子受体（FGFR）是与乳腺癌有关的酪氨酸激酶受体。本研究的目的是评估FGFR-1、-2、-3和-4蛋白在正常小鼠乳腺发育以及小鼠和人乳腺癌中的表达。利用免疫组化和Western blot技术，我们报告了出生后乳腺发育过程中FGFR的激素调节。孕激素治疗成年处女乳腺导致FGFR-3从细胞质到细胞核的定位发生变化，而17-β-雌二醇治疗则诱导FGFR-2和-3的表达和/或定位发生变化。在表现出不同程度的激素依赖性的小鼠乳腺癌中，我们发现孕激素诱导的表达增加，主要是FGFR-2和-3。这些受体在非依赖性变体中组成性激活。我们研究了三种作为异种移植物生长的管腔型人乳腺癌细胞系，它们特别表达FGFR-2和-3，表明激素状态和FGFR表达之间存在相关性。最重要的是，在来自58名患者的乳腺癌样本中，我们发现FGFR-2和FGFR-3表达之间存在强相关性（P < 0.01;斯皮尔曼相关性），而每种受体与雌激素受体表达的相关性较弱。FGFR-4与c-erbB 2过表达相关。我们的结论是，FGFR-2和-3可能是机械联系，并可能成为治疗雌激素受体阳性乳腺癌患者的潜在目标。
Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-beta-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P < 0.01; Spearman correlation) between FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.