Loss of maspin expression is associated with development and progression of gastric carcinoma with p53 abnormality.
Loss of maspin expression is associated with development and progression of gastric carcinoma with p53 abnormality.
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DOI：
10.3892/or.12.5.985
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发表时间：
2004-11
期刊：
影响因子：
4.2
通讯作者：
R. Ito;H. Nakayama;Kazuhiro Yoshida;N. Oda;W. Yasui
中科院分区：
文献类型：
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作者：
R. Ito;H. Nakayama;Kazuhiro Yoshida;N. Oda;W. Yasui
Maspin是一种与丝氨酸蛋白酶抑制剂家族相关的丝氨酸蛋白酶抑制剂，最初在正常乳腺上皮中发现。maspin的表达降低与某些人类肿瘤的发生、侵袭和转移有关。本研究采用免疫组化和RT-PCR方法检测maspin在胃粘膜、腺瘤和胃癌中的表达。在非肿瘤性胃粘膜中，maspin表达于胃小凹上皮、胃底腺细胞和幽门腺细胞的胞浆和胞膜。Maspin在胃癌和腺瘤中的表达缺失率分别为71%（71/100）和19%（4/21）。maspin表达缺失与低分化、晚期和浸润深度有关（P<0.001）。maspin的表达与p53的异常聚集呈负相关。用去甲基化剂5-aza-2 '-deoxycytidine处理后，8个胃癌细胞系中有5个细胞系的Maspin mRNA表达全部丢失。结果提示，maspin基因表达缺失可能与p53通路有关，可能参与了胃癌的发生、发展。maspin表达缺失可作为高度恶性肿瘤的生物学标志物。
Maspin, a serine protease inhibitor related to the serpin family, was originally identified in normal mammary epithelium. Reduced expression of maspin is related with development, invasion and metastasis of certain human cancers. In the present study, the expression of maspin was examined in gastric mucosa, adenoma and carcinoma by immunohistochemistry and RT-PCR. In non-neoplastic mucosa, maspin was expressed in cytoplasm and cell membrane of foveolar epithelia, fundic glandular cells and pyloric glandular cells. Maspin expression was lost in 71% (71/100) of gastric carcinomas, and in 19% (4/21) of adenomas, respectively. Loss of maspin expression was significantly associated with poorly differentiated histology, advanced stage and deep invasion (P<0.001). There was an inverse correlation between maspin expression and abnormal p53 accumulation. Maspin mRNA expression was lost in all of 8 gastric carcinoma cell lines that was retrieved after treatment with demethylation agent 5-aza-2'-deoxycytidine in 5 of 8 cell lines. These results suggest that loss of maspin expression partly due to DNA methylation may participate in tumor development and progression of gastric carcinoma in relation with p53 pathway. Loss of maspin expression may serve as a biological marker of high-grade malignancy.