Sozzi G, Tornielli S, Tagliabue E, Sard L, Pezzella F, Pastorino U, Minoletti F, Pilotti S, Ratcliffe C, Veronese M L, Goldstraw P, Huebner K, Croce C M, Pierotti M A
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Cancer Res. 1997 Dec 1;57(23):5207-12.
Genomic alterations and abnormal expression of the FHIT gene at 3p14.2 have been observed in cell lines and primary tumors of the lung. To correlate FHIT locus DNA and RNA lesions with effects on Fhit protein expression, we have analyzed 11 lung cancer cell lines, 15 small cell lung carcinomas, and 38 pairs of non-small cell primary tumors and bronchial mucosa specimens by molecular genetic and immunocytochemical methods. Using specific antibodies against the Fhit protein, we observed concordance between RNA abnormalities and lack of Fhit protein expression in lung tumors and cell lines. In addition, absence of Fhit protein in some precancerous dysplastic lesions suggested that FHIT inactivation may occur at an early phase of lung carcinogenesis.
在肺癌的细胞系和原发性肿瘤中已观察到3p14.2处FHIT基因的基因组改变及异常表达。为了将FHIT基因座的DNA和RNA损伤与对Fhit蛋白表达的影响相关联,我们采用分子遗传学和免疫细胞化学方法分析了11个肺癌细胞系、15个小细胞肺癌以及38对非小细胞原发性肿瘤和支气管黏膜标本。使用针对Fhit蛋白的特异性抗体,我们观察到肺肿瘤和细胞系中RNA异常与Fhit蛋白表达缺失之间存在一致性。此外,在一些癌前发育异常病变中缺乏Fhit蛋白,这表明FHIT失活可能发生在肺癌发生的早期阶段。