Wang C, Thor A D, Moore D H, Zhao Y, Kerschmann R, Stern R, Watson P H, Turley E A
Department of Anatomy and Cell Biology, University of Toronto, and The Hospital for Sick Children, Ontario, Canada.
Clin Cancer Res. 1998 Mar;4(3):567-76.
RHAMM is an oncogene that regulates signaling through ras and controls mitogen-activated protein kinase [extracellular signal-regulated protein kinase (ERK)] expression in embryonic murine fibroblasts. ERK is a dual-specificity kinase that controls expression of proteins relevant to tumorigenesis, proliferation, and motility. To assess whether RHAMM and ERK are involved in human breast tumor progression, we examined RHAMM, ras, and ERK expression in two cohorts of breast cancer patients using reverse transcription-PCR and immunocytochemistry. We show that overexpression of RHAMM in primary tumors of two patient cohorts was significantly prognostic of poor outcome in breast cancer progression. Furthermore, RHAMM overexpression occurred within subsets of tumor cells in the primary tumor, and this staining pattern was associated with lymph node metastases. The metastases exhibited a significantly higher level of staining for RHAMM than did the primary tumor. RHAMM expression strongly correlated with overexpression of both ras and ERK, although overexpression of either of these two signaling molecules was not by itself a prognostic indicator. These results identify a new parameter that is involved in lymph node metastasis of primary breast cancers and suggest that quantification of RHAMM overexpression may be a useful prognostic indicator for breast carcinoma progression.
透明质酸介导运动受体（RHAMM）是一种癌基因，它通过Ras调节信号传导，并控制胚胎小鼠成纤维细胞中丝裂原活化蛋白激酶[细胞外信号调节蛋白激酶（ERK）]的表达。ERK是一种双特异性激酶，可控制与肿瘤发生、增殖和运动相关的蛋白质表达。为了评估RHAMM和ERK是否参与人类乳腺肿瘤进展，我们使用逆转录聚合酶链反应（RT-PCR）和免疫细胞化学方法检测了两组乳腺癌患者中RHAMM、Ras和ERK的表达。我们发现，在两组患者的原发性肿瘤中，RHAMM的过表达是乳腺癌进展不良预后的显著指标。此外，RHAMM过表达发生在原发性肿瘤的部分肿瘤细胞中，这种染色模式与淋巴结转移相关。转移灶中RHAMM的染色水平明显高于原发性肿瘤。RHAMM表达与Ras和ERK的过表达密切相关，尽管这两种信号分子单独过表达均不是预后指标。这些结果确定了一个参与原发性乳腺癌淋巴结转移的新参数，并表明RHAMM过表达的定量分析可能是乳腺癌进展的一个有用的预后指标。
