Study for molecular mechanism of human lung adenocarcinoma.

三年来，我们主要开展了以下三个方面的研究工作，旨在阐明肺腺癌发生和发展的分子机制。1.应用抑制性消减杂交技术比较4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone诱导的A/J小鼠腺瘤和正常肺组织的表达谱。肺表面活性物质相关蛋白A(SP-A)和溶菌酶的mRNAs在肺腺瘤组织中的转录水平明显高于正常肺组织。2.建立了永生化的人非典型腺瘤性增生(AAH)细胞系(PL16T)和来自同一患者的人非肿瘤性支气管上皮细胞系(PL16B)。用SSH方法比较PL16T和PL16B的表达谱。在PL16T中检测到肿瘤相关钙信号转导蛋白2(TACSTD2)和S100钙结合蛋白A2(S100A2)的高转录。我们的研究结果表明，TACSTD2和S100A2在肺腺癌的侵袭前期AAH中选择性地高表达，并持续高表达，直到病变进展到细支气管肺泡癌(BAC)，后者是人类肺腺癌的原位阶段和更晚期。3.利用人肺腺癌病例的切除材料，用SSH方法比较了野口C型腺癌(早期和晚期细支气管肺泡癌)和同一病例的原位病变组织中晚期区的表达情况。进展期病变中Bax抑制因子-1(BI-1)、TACSTDI、线粒体细胞色素C氧化酶II和FJL12770的转录水平显著升高。BAC和有细支气管肺泡(BA)扩散的癌组织中BI-1基因表达显著高于无BA成分的癌组织。BI-1基因的表达仅限于恶性生长的肿瘤细胞。

For the three years, we mainly performed the following three research projects to make clear the molecular mechanisms of the pathogenesis and the malignant progression of the lung adenocarcinoma.1.The expression profile of adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse was compared with that of normal lung tissue by suppression subtractive hybridization (SSH). The mRNAs of surfactant-associated protein A (SP-A) and lysozyme showed characteristically higher transcription in the adenoma tissue than normal lung.2.We established an immortalized human atypical adenomatous hyperplasia (AAH) cell line (PL16T) and a human non-neoplastic bronchial epithelial cell line (PL16B) from the same patient. The expression profile of PL16T was compared with that of PL16B by SSH method. The characteristically high transcription of tumor-associated calcium signal transducer 2 (TACSTD2) and S100 calcium binding protein A2 (S100A2) was detected in PL16T. Our findings indicate that TACSTD2 and S100A2 are selectively and highly expressed in AAH, which is preinvasive stage of lung adenocaricnoma, and the high expression is preserved until the lesion progresses to bronchioloalveolar carcinoma (BAC), which is in situ stage of human lung adenocarcinoma and more advanced stages.3.Using the resected material of human lung adenocarcinoma case, the expression profile of advanced area in Noguchi type C adenocarcinoma (early but advanced bronchioloalveolar carcinoma) was compared with that of in situ lesion of the same case by SSH method. The significantly high transcription of Bax inhibitor-1 (BI-1), TACSTDI, mitochondrial cytochrome c oxidase II, and FJL12770 was detected in adnvanced lesion. The BI-1 gene expression in tumor specimens was significantly higher in BAC and carcinoma with bronchioloalveolar (BA) spreading than carcinomas without BA component. The BI-1 gene expression was restricted to the tumor cells with lepidic growth.