乳腺癌组织中多形上皮黏蛋白1表达与肿瘤侵袭力的研究

目的　探讨多形上皮黏蛋白 1 (mucin1 )表达异常与乳腺癌细胞侵袭力的关系。方法　应用免疫组织化学方法检测 97例乳腺肿瘤组织中mucin1的表达。乳腺癌细胞株MCF 7转染反义寡核苷酸(ASODN)后,应用逆转录 聚合酶链反应 (RT -PCR)检测mucin1mRNA,应用流式细胞术检测mucin1表达阳性率,细胞侵袭实验检测细胞侵袭力。结果　mucin1在癌旁正常乳腺组织和乳腺良性肿瘤组织中均为细胞顶膜阳性表达,而在早期乳腺癌 (30例 )、乳腺浸润性癌 (18例 )、乳腺癌淋巴结转移灶(17例)中为整个细胞膜阳性表达。与乳腺原位癌相比,微小浸润癌的mucin1表达强度升高(P=0. 04),而乳腺浸润性癌与乳腺癌淋巴结转移灶之间mucin1表达强度差异无统计学意义(P=0. 56)。转染ASODN的乳腺癌细胞株,其mucin1mRNA和mucin1蛋白表达率显著下降 (P<0. 05),细胞侵袭实验中,侵袭细胞数明显减少(P<0 .05),正义组实验细胞无类似改变。结论　乳腺癌细胞mucin1在细胞膜的异常分布及表达升高可促使癌细胞间相互排斥而易于向周围侵袭生长,但该异常表达可能与其淋巴道转移关系不大。针对mucin1mRNA的ASODN可抑制乳腺癌细胞的侵袭能力。

Expression of mucin 1 and tumor invasiveness in breast carcinoma

OBJECTIVE: To study the relationship of abnormal expression of mucin 1 with the invasiveness of breast carcinoma cells. METHODS: Immunohistochemistry was used to detect the protein expression of mucin 1 in 5 specimens of juxta-cancerous normal tissues, 20 specimens of benign breast tumors, 35 specimens of early breast carcinoma, 22 specimens of infiltrating cancerous tissues, and 20 specimens of lymph node foci with metastatic breast carcinoma. Human breast cancer cells of the line MCF-7 were cultured and transfected with antisense oligodeoxynucleotide (ASODN) of mucin 1. The mucin 1 mRNA expression in the cells was detected by RT-PCR and the protein expression of mucin 1 in the cells was detected by flow cytometry. The cell invasiveness was detected by Matrigel invasion assays. RESULTS: Top membrane positive expression of mucin 1 was observed in the normal breast tissues and breast benign tumors and whole membrane positive expression of mucin 1 was observed in the 30 of the 35 specimens of early breast carcinoma, 18 of the 22 specimens of breast infiltrating carcinoma, and 17 of the 20 specimens of lymph node metastatic tissues. The mRNA and protein expressions of mucin 1 in the breast carcinoma cells treated with ASODN of mucin 1 were significantly decreased (both P < 0.05). The number of invasive cells decreased significantly in the cell treated with ASODN of mucin 1 in comparison with those treated with sense nucleotide (P < 0.05). CONCLUSION: The abnormal distribution of mucin 1 contributes to the invasiveness of carcinoma cells and may not make difference in the lymphogenous metastasis of the carcinoma. The invasiveness of breast carcinoma cells can be inhibited by the ASODN complementary to the start site of mucin1 mRNA.