Poola Indira, Abraham Jessy, Liu Aiyi, Marshalleck Josephine J, Dewitty Robert L
Department of Surgery and Breast Center and.
Breast Cancer (Auckl). 2008;1:65-78. doi: 10.4137/bcbcr.s557. Epub 2008 Apr 17.
GPR30 is a cell surface estrogen receptor that has been shown to mediate a number of non-genomic rapid effects of estrogen and appear to balance the signaling of estrogen and growth factors. In addition, progestins appear to use GPR30 for their actions. Therefore, GPR30 could play a critical role in hormonal regulation of breast epithelial cell integrity. Deregulation of the events mediated by GPR30 could contribute to tumorigenesis.
To understand the role of GPR30 in the deregulation of estrogen signaling processes during breast carcinogenesis, we have undertaken this study to investigate its expression at mRNA levels in tumor tissues and their matched normal tissues. We compared its expression at mRNA levels by RT quantitative real-time PCR relative to GAPDH in ERα"-positive (n = 54) and ERα"-negative (n = 45) breast cancer tissues to their matched normal tissues.
We report here, for the first time, that GPR30 mRNA levels were significantly down-regulated in cancer tissues in comparison with their matched normal tissues (p < 0.0001 by two sided paired t-test). The GPR30 expression levels were significantly lower in tumor tissues from patients (n = 29) who had lymph node metastasis in comparison with tumors from patients (n = 53) who were negative for lymph node metastasis (two sample t-test, p < 0.02), but no association was found with ERα, PR and other tumor characteristics.
Down-regulation of GPR30 could contribute to breast tumorigenesis and lymph node metastasis.
GPR30是一种细胞表面雌激素受体,已被证明可介导雌激素的多种非基因组快速效应,并且似乎能平衡雌激素和生长因子的信号传导。此外,孕激素似乎也通过GPR30发挥作用。因此,GPR30可能在乳腺上皮细胞完整性的激素调节中起关键作用。GPR30介导的事件失调可能促成肿瘤发生。
为了解GPR30在乳腺癌发生过程中雌激素信号传导过程失调中的作用,我们开展了本研究,以调查其在肿瘤组织及其配对正常组织中的mRNA水平表达。我们通过RT定量实时PCR,相对于甘油醛-3-磷酸脱氢酶(GAPDH),比较了雌激素受体α(ERα)阳性(n = 54)和ERα阴性(n = 45)乳腺癌组织及其配对正常组织中GPR30在mRNA水平的表达。
我们首次在此报告,与配对的正常组织相比,癌组织中GPR30的mRNA水平显著下调(双侧配对t检验,p < 0.0001)。与无淋巴结转移患者的肿瘤(n = 53)相比,有淋巴结转移患者(n = 29)的肿瘤组织中GPR30表达水平显著降低(两样本t检验,p < 0.02),但未发现与ERα、孕激素受体(PR)及其他肿瘤特征有关联。
GPR30的下调可能促成乳腺肿瘤发生和淋巴结转移。