FHIT protein expression during malignant transformation of human bronchial epithelial cells induced by NNK

Abstract

Most studies about FHIT protein expression were performed in normal tracheal epithelium, precancerous lesions and lung cancer tissues respectively, but not in the course of malignant transformation of lung cancer. The aim of this study is to detect the changes of FHIT protein expression during malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) induced by tobacco-specific nitrosamine (NNK), and to explore its significance. BEAS-2B cells were induced to malignantly transform (BEAS-2B NNK) by 500mg/L NNK, and FHIT protein expression was detected in the different passages of BEAS-2B NNK and BEAS-2B cells by SP immunocytochemistry. Part 1: Model of malignant transformation of BEAS-2B cells induced by NNK was established. (1) The serum resistance was significantly increased in the 5th passage of BEAS-2B NNK cells. (2) The anchorage independent growth (soft agar colony formation) appeared in the 15th passage of BEAS-2B NNK cells. (3) The ultrastructure of the 20th passage of BEAS-2B NNK cells showed obvious heteromorphy characterization. (4) The 25th passage of BEAS-2B NNK cells developed into tumors in nude mice, which were well differentiated squamous cell carcinoma. Part 2: FHIT protein was steadily expressed in the different passages of BEAS-2B cells (P > 0.05). FHIT protein expression was obviously decreased from 5th to 15th passage of BEAS-2B NNK cells, but it was unexpectedly overexpressed in the 25th passage. (1) The model of malignant transformation of BEAS-2B cells induced by NNK (500mg/L) can be established successfully and may be used for investigation of molecular biological mechanisms of lung cancer, especially for smoking-related cases. (2) Decrease of FHIT protein expression might be an early event, however, its overexpression in the late passages should be further studied.