染色体维持蛋白5、7在甲状腺间变细胞癌中的表达及生物学意义

Expression of minichromosomes maintain protein 5, 7 in anaplastic thyroid carcinoma and its biological research

目的对比分析在甲状腺间变细胞癌（anaplastic thyroid carcinoma，ATC）、正常的甲状腺（nor mal thyroid，NT）及PTC组织中染色体维持蛋白（minichromosome maintenance proteins，MCM）的表达情况及生物学意义。方法免疫组化检测NT、ATC、PTC3种组织切片和ATC细胞中MCM5、MCM7及增殖细胞核抗原（PCNA）的表达量，Western blot、Northern blot检测MCM复合物的表达量，应用siRNA技术干扰MCM7的表达。结果在ATC癌组织中，MCM5呈高表达状态占全部患者的65％，MCM7呈高表达状态占全部患者的73％，而NT组织及胛C组织中MCM5及MCM7表达极低。在ATC细胞中MCM5和MCM7的高表达同时伴随MCM2和MCM6的表达升高。用小干扰RNA抑制MCM7的蛋白表达水平会降低ATC细胞中DNA的合成效率。结论在ATC中MCM蛋白的表达上调并引起ATC的过度增殖。

Objective To cast light on the mechanisms governing anaplastic thyroid carcinoma （ATC） and to evaluate the minichromosomes maintain protein （MCM） 5 and MCM7 expression in human normal thyroid （NT）, papillary thyroid carcinoma （PTC）, and ATC samples, as well as in primary culture cells. Methods We tested the expression of MCM5, MCM7and PCNA in NT, PTC and ATC by immunohistochemistry. We used Western blot and Northern blot to test the expression of MCMS, and MCMT. ATC cells were transfected with MCM7 siRNA, and Western blot was used to examine the change of the expression of MCM7. Results In ATC samples, MCM5 had high expression in 65% patients, and MCM7 had high expression in 73% patients. The ex- pression of MCM5 and MCM7 in NT and PTC samples were very low which can be ignored. In ATC cells, high MCM5 and MCM7 expression was paralleled by high levels of MCM2 and MCM6. Inhibition of MCM7 protein levels by small inhibitory duplex RNAs could reduce the rate of DNA synthesis in ATC ceils. Conclusion MCM protein expression is upregulated in ATC and leads to excessive proliferation of ATC.