肺泡样肺腺癌中端锚聚合酶的表达及其与WNT信号通路的关系

Tankyrase expression in lung bronchiolo-alveolar adenocarcinoma and its relationship with the WNT pathway

目的探讨肺泡样肺腺癌中端锚聚合酶(TNKS)的表达情况及其与WNT信号通路的关系。方法收集72例单一亚型肺泡样肺腺癌组织(肺腺癌组)和67例癌旁正常肺组织(癌旁组)标本,应用免疫组化法检测2组TNKS、β-连环蛋白(β-catenin)和c-myc蛋白的表达情况,并分析3种蛋白在肺腺癌组织中表达的相关性。Westernblot检测TNKS在肺腺癌组和癌旁组中表达的差异性。结果 TNKS蛋白主要于细胞质表达;β-catenin蛋白在肺腺癌组主要于细胞质和细胞核表达,β-catenin在癌旁组主要于细胞质表达,少量于细胞核表达;c-myc蛋白主要于细胞核表达。TNKS、β-catenin和c-myc蛋白在肺腺癌组中的阳性表达率均高于癌旁组(P<0.05)。β-catenin蛋白细胞质和细胞核中的表达与TNKS及c-myc的表达水平均呈正相关(均P<0.05)。Western blot检测示TNKS在肺腺癌组中的相对表达水平高于癌旁组(0.497±0.021 vs.0.237±0.015,t=13.00,P<0.01)。结论 TNKS在肺腺癌中异常高表达,可能是通过调控WNT信号通路,从而促进肺腺癌的发生,抑制TNKS表达或可成为治疗肺腺癌的新靶点。

Objective To explore the expression of tankyrase (TNKS) and its relationship with WNT/β-catenin signal?ing pathway in lung acinar adenocarcinoma. Methods Seventy-two samples of single subtype alveolar like lung adenocarci?noma (lung adenocarcinoma group) and 67 specimens of normal lung tissue adjacent to carcinoma (adjacent to carcinoma group) were collected. Immunohistochemical method was used to detect expressions of TNKS, beta-catenin (β-catenin) and c-myc protein. The correlation of each protein expression in lung adenocarcinoma tissues was analyzed. The differential ex?pression of TNKS was detected by Western blot assay in two groups. Results Tankyrase protein was mainly expressed in cy?toplasm. The expression ofβ-catenin protein was mainly in cytoplasm and nuclear of lung adenocarcinoma. The expression ofβ-catenin was mainly in cytoplasm, and a small amount was in nuclear of the adjacent group. The c-myc protein was ex?pressed mainly in the nucleus. The positive expression rates of TNKS,β-catenin and c-myc protein were significantly high?er in lung adenocarcinoma group than those of adjacent to carcinoma group (P<0.05). The expression ofβ-catenin in cyto?plasm and nucleus was positively correlated with the expression of TNKS and c-myc (P<0.05). Western blot analysis showed that the relative expression level of TNKS was significantly higher in lung adenocarcinoma group than that of adja?cent to carcinoma group (0.497 ± 0.021 vs. 0.237 ± 0.015, t=13.00, P<0.01). Conclusion Abnormally high expression of TNKS in lung adenocarcinoma may promote the occurrence of lung cancer by regulating the WNT signaling pathways. Inhib?iting TNKS expression may become a new target to treat lung adenocarcinoma.