ER-activating ability of breast cancer stromal fibroblasts is regulated independently of alteration of TP53 and PTEN tumor suppressor genes
ER-activating ability of breast cancer stromal fibroblasts is regulated independently of alteration of TP53 and PTEN tumor suppressor genes
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DOI：
10.1016/j.bbrc.2012.10.035
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发表时间：
2012-11-16
影响因子：
3.1
通讯作者：
Yamaguchi, Yuri
中科院分区：
文献类型：
--
作者：
Suda, Tetsuji;Oba, Hanako;Yamaguchi, Yuri
癌相关成纤维细胞（CAFs）与肿瘤的进展和转移有关，并且能够激活乳腺癌中的雌激素受体（ER）。我们建立了人乳腺癌细胞系的稳定转化体来检测CAF特异性ER激活能力，并发现这种CAF能力在肿瘤之间存在差异。一些研究报道了基质细胞中肿瘤抑制基因的高频率改变，但通常不同意频率。此外，CAF诱导的雌激素信号的激活机制，包括这些基因畸变的影响，还没有完全理解。我们研究了20例乳腺癌患者CAFs中肿瘤抑制基因畸变和ER激活能力的相关性。尽管CAF特异性ER激活能力在个体病例中存在差异，但所有CAF均保持753和PTEN的野生型等位基因。此外，在任何CAF中均未观察到这些基因的拷贝数畸变。我们的研究结果表明，ER激活能力的CAFs的调节独立于这些基因的畸变：和肿瘤间质相互作用的其他机制可能会影响乳腺癌雌激素信号的激活。(C)2012 Elsevier Inc. All rights reserved.
Carcinoma-associated fibroblasts (CAFs) are associated with tumor progression and metastasis, and are able to activate estrogen receptor (ER) in breast cancer. We established a stable transformant of a human breast cancer cell line to detect CAF-specific ER-activating ability, and found that this CAF ability varied among tumors. Some studies have reported a high frequency of alterations among tumor suppressor genes in stromal cells, but do not generally agree as to the frequency. Moreover, the activation mechanism of CAF-induced estrogen signals, including the effects of these gene aberrations, is not fully understood. We investigated the relevance of tumor suppressor gene aberrations and ER-activating ability in CAFs derived from 20 breast cancer patients. Although CAF-specific ER-activating abilities varied among individual cases, all CAFs maintained wild-type alleles for 753 and PTEN. Also, copy number aberrations in these genes were not observed in any CAFs. Our results suggest that the ER-activating ability of the CAFs is regulated independently of aberrations in these genes: and that other mechanisms of tumorstromal interaction may affect activation of estrogen signals in breast cancer. (C) 2012 Elsevier Inc. All rights reserved.