Collapsin response mediator protein 2 is involved in regulating breast cancer progression
Collapsin response mediator protein 2 is involved in regulating breast cancer progression
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DOI：
10.1007/s12282-013-0447-5
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发表时间：
2014-11-01
期刊：
影响因子：
4
通讯作者：
Goshima, Yoshio
中科院分区：
文献类型：
--
作者：
Shimada, Kazuhiro;Ishikawa, Takashi;Goshima, Yoshio
已经报道了在几种恶性肿瘤中改变表达的胰蛋白酶反应介导蛋白（CRMPs），包括在肺癌中下调CRMP 1和在结直肠癌中上调CRMP 2。为探讨CRMP mRNA在乳腺癌组织中的表达及其与临床病理特征的关系，采用免疫组化法检测22例乳腺癌组织和4例正常乳腺组织中CRMP mRNA的表达。通过实时定量逆转录聚合酶链反应分析乳腺癌标本亚组中每种CRMP（CRMP 1 -5）mRNA的平均表达水平，并与正常乳腺组织进行比较。此外，173例乳腺癌标本和匹配的正常乳腺对照用于免疫组织化学的基础上的组织芯片技术。结果：CRMP 2 mRNA在乳腺癌组织中的表达明显降低，而其他CRMPs在正常乳腺组织和乳腺癌组织中的表达无明显差异。免疫组化显示CRMP 2蛋白在乳腺癌组织中的表达也明显降低（P < 0.001）。磷酸化的CRMP 2在乳腺癌细胞核中表达，而在正常乳腺细胞核中未见表达（P < 0.001）。此外，核磷酸化CRMP 2表达随组织学分级和三阴性亚型的增加而增加，核磷酸化CRMP 2表达减少和核磷酸化CRMP 2表达增加可能与乳腺癌的进展有关。
Altered expression of collapsin response mediator proteins (CRMPs) has been reported in several malignant tumors, including downregulation of CRMP1 in lung cancer and upregulation of CRMP2 in colorectal cancer. This study aimed to investigate the relationship between CRMP expression and clinicopathological characteristics in patients with breast cancer.Twenty-two breast cancer and four normal breast tissues were used to assess CRMP mRNA expression. The average expression level of each CRMP (CRMP1-5) mRNA was analyzed in a subset of breast cancer specimens and compared with that in normal breast tissue by real-time quantitative reverse-transcription polymerase chain reaction. Furthermore, 173 breast cancer specimens and matching normal breast controls were used for immunohistochemistry based on the tissue microarray technique. Levels of CRMP2 and phosphorylated CRMP2 protein were assessed, and possible correlations between the clinicopathological characteristics were evaluated.The expression of CRMP2 mRNA was significantly decreased in breast cancer tissues, while that of the other CRMPs was similar between normal and breast cancer tissues. Immunohistochemistry revealed that CRMP2 protein expression was also decreased in breast cancer tissues (P < 0.001). Phosphorylated CRMP2 was observed in the nuclei of breast cancer cells but not in normal mammary cells (P < 0.001). Furthermore, nuclear phosphorylated CRMP2 expression was increased in proportion to the histological grade and triple-negative subtype.Reduced CRMP2 expression and elevated expression of nuclear phosphorylated CRMP2 may be associated with breast cancer progression.