端粒酶逆转录酶及其调控因子在非小细胞肺癌组织中的表达及意义

Expression and Significance of Telomerase Reverse Transcriptase and Its Regula tors in Non-Small Cell Lung Carcinoma

背景与目的:端粒酶是一种核糖核蛋白复合物,在正常机体细胞中不表达,而在一系列调节因子的作用下被激活,导致肿瘤的发生。作为端粒酶活性的关键决定因子,端粒酶逆转录酶的调控研究已取得了重大进展,但具体机制仍不清楚。本研究探讨人端粒酶逆转录酶(humantelomerasereversetranscriptase,hTERT)mRNA与其有关调控因子c-myc、突变型p53、蛋白激酶Cα(proteinkinaseCalpha,PKCα)间的关系,以及4种指标在非小细胞肺癌(non-smallcelllungcarcinoma,NSCLC)中表达的临床病理意义。方法:采用原位杂交法检测113例NSCLC组织中hTERTmRNA的表达,采用SP免疫组化法检测c-myc、突变型P53、PKCα的表达。结果:113例NSCLC中hTERTmRNA、c-myc、突变型P53和PKCα的检出率分别为80.5%、68.1%、61.9%、85.0%。hTERTmRNA与c-myc、PKCα之间相关性有统计学意义;突变型P53与hTERTmRNA、c-myc和PKCα的表达之间均无相关性。突变型P53的表达与肿瘤细胞的分化程度有关,其阳性率随着肿瘤细胞分化的恶性程度增加而逐渐增加(P<0.05)。hTERTmRNA、c-myc和PKCα与肿瘤细胞的分化程度无关(P>0.05)。4种指标的表达与肿瘤的组织学类型、TNM分期及淋巴结转移状况无关。结论:C-myc及PKCα与端粒酶的表达有关。

BACKGROUND & OBJECTIVE: Telomerase is a ribonucleoprotein complex , which is silent in normal human somatic cells but may be reactivated by a seri es of regulators, and cause tumorigenesis. As a critical factor of telomerase ac tivity, much progression has been achieved in the study of regulation of human t elomerase reverse transcriptase, but the detail mechanism is still not clear. Th is study was designed to investigate the relationship of expression of human tel omerase reverse transcriptase mRNA (hTERT mRNA) and its regulators including c- myc, mutant p53, protein kinase C alpha (PKCα) with clinicopathological signifi cance of expression of the four markers in non-small cell lung carcinoma (NSCLC ). METHODS: The expression of hTERT mRNA in 113 NSCLC specimens were detected by in situ hybridization, and the expression of c-myc, mutant p53, and PKCα in the same specimens were detected by immunohistochemistry. RESULTS: The positive rates of 113 NSCLC samples for hTERT mRNA, c-myc, mutant p53, and PKCα were 8 0.5%, 68.1%, 61.9%, and 85.0%, respectively. The differences were statistica lly significant among the expression of hTERT mRNA, c-myc, and PKCα (P< 0 .05 or P< 0.01), but was not significant between the expression of mutant p53 an d hTERT mRNA, c-myc as well as PKCα. The expression of mutant p53 was associat ed with carcinoma cell differentiation (P< 0.05), and its positive rate graduall y increased with the extend of differentiation of carcinoma cell. The expression of hTERT mRNA, c-myc, and PKCα were not associated with carcinoma cell diffe rentiation. There was no relationship of expression of the four markers with his tological types, TNM stages, and lymph node metastasis status. CONCLUSION: C-my c and PKCα were associated with the expression of telomerase.