Bolon I, Gouyer V, Devouassoux M, Vandenbunder B, Wernert N, Moro D, Brambilla C, Brambilla E
Airways and Lung Cancer Research Group, Institute A. Bonniot, Faculté de médecine, Grenoble, France.
Am J Pathol. 1995 Nov;147(5):1298-310.
The c-ets-1 transcription factor has been involved in the in vitro transactivation of matrix-degrading protease genes that might play an important role in tumor invasion. Using in situ hybridization, we analyzed serial frozen sections for c-ets-1, collagenase 1, and urokinase-type plasminogen activator gene expression in 54 lung carcinomas including 34 non-neuroendocrine carcinomas (18 squamous carcinomas, 10 adenocarcinomas, 3 large cell carcinomas, and 3 basaloids) and 20 neuroendocrine carcinomas (7 small cell lung carcinomas, 4 large cell neuroendocrine carcinomas, 4 well differentiated neuroendocrine carcinomas, and 5 carcinoids). c-ets-1 gene was expressed in stromal cells in 44/54 lung carcinomas including one metastasizing carcinoid. c-ets-1 transcripts were also detected in cancer cells more frequently in neuroendocrine than in non-neuroendocrine carcinomas (P = 0.0059) and in stages III and IV and metastasis more frequently than in stages I and II ( P = 0.0065). Collagenase 1 gene was expressed in 16/34 non-neuroendocrine tumors and in 1/20 neuroendocrine tumors, either in stromal (12/17) or in cancer cells (6/17). Urokinase-type plasminogen activator mRNAs were expressed in 45/54 lung carcinomas in stromal and/or cancer cells. In non-neuroendocrine tumors, c-ets-1 and collagenase 1 gene expressions in stromal cells were correlated. These results demonstrate that the transcription factor c-ets-1, collagenase 1, and urokinase-type plasminogen activator are involved in lung cancer invasion and suggest that c-ets-1 protein might transactivate collagenase 1 gene during tumor invasion.
c-ets-1转录因子参与了基质降解蛋白酶基因的体外反式激活，这些基因可能在肿瘤侵袭中发挥重要作用。我们采用原位杂交技术，分析了54例肺癌连续冰冻切片中c-ets-1、胶原酶1和尿激酶型纤溶酶原激活剂基因的表达情况，其中包括34例非神经内分泌癌（18例鳞状细胞癌、10例腺癌、3例大细胞癌和3例基底样癌）和20例神经内分泌癌（7例小细胞肺癌、4例大细胞神经内分泌癌、4例高分化神经内分泌癌和5例类癌）。在54例肺癌中的44例包括1例转移性类癌的基质细胞中表达了c-ets-1基因。在神经内分泌癌中，癌细胞中检测到c-ets-1转录本的频率高于非神经内分泌癌（P = 0.0059），在III期和IV期及转移患者中比I期和II期更频繁（P = 0.0065）。胶原酶1基因在34例非神经内分泌肿瘤中的16例以及20例神经内分泌肿瘤中的1例表达，可在基质细胞（12/17）或癌细胞（6/17）中表达。尿激酶型纤溶酶原激活剂mRNA在54例肺癌的基质和/或癌细胞中表达。在非神经内分泌肿瘤中，基质细胞中c-ets-1和胶原酶1基因表达相关。这些结果表明，转录因子c-ets-1、胶原酶1和尿激酶型纤溶酶原激活剂参与肺癌侵袭，并提示c-ets-1蛋白可能在肿瘤侵袭过程中反式激活胶原酶1基因。
