Defective expression of FasL and Bax in human lung cancer.

Abstract

The present studies investigated whether FasL and Bax genes are expressed in pleuro-pulmonary biopsies from patients with lung cancer. FasL, Bax, and TNFalpha mRNAs were detected in 19 biopsies of primary or metastasic lung cancer by fluorescent in situ hybridization assays. Fluorescent probes were produced by polymerase chain reaction using a human spleen lambda gt11 library and specific primers for FasL, Bax, and TNFalpha. Proteins were detected by immunohistochemistry using monoclonal anti- FasL, anti-Bax, and anti-TNFalpha antibodies. Chromatin fragmentation was detected by TUNEL. Seven negative samples from subjects without lung pathology were obtained during legal autopsies and 12 positive control biopsies from patients with lung infections were also included. Sixty-eight percent of lung cancer biopsies exhibited FasL; Bax was expressed in 68% and TNFalpha in 63%. FasL protein was detected in 21%, Bax protein in 26%, and TNFalpha was present in 31% of cancer biopsies. A low degree of apoptosis in lung cancer was demonstrated by TUNEL assays. A defect in FasL, Bax, and TNFalpha gene expression was found in lung cancer biopsies. Some tumors normally expressed the mRNA of FasL, Bax, or TNFalpha, but their proteins were absent, or were non-functional, since TUNEL assays were negative. Such a failure would contribute to cancer cell survival and dissemination.