Molecular Cytogenetic Alterations In The Early Stage Of The Carcinogenesis Of Human Bronchial Epithelial Cells

Lung cancer is one of the most common cancers in the world, and its incidence is still increasing. Clarification of the molecular and cytogenetic mechanism during the development of the lung cancer, would be useful for the prevention, early diagnosis and therapy of human lung cancers.NSCLC ( non-small cell lung cancer) originates mainly from bronchial epithelial cells, and represents the majority of human lung cancers. We have developed an effective culture system for bronchial epithelial cells and lung cancer cells. Four cases of immortalized human bronchial epithelial cell lines were established by transfection of plasmid containing the early region of SV40. Some molecular and cytogenetic alterations were found in one immortalized bronchial epithelial cell line which was approching to malignant transformation. The other 3 bronchial epithelial cell lines, two NSCLC cell lines and 12 cases of clinic NSCLC biopsies and their adjacent bronchial epithelia were studied. The results are summarized as follows:1. Activation of c-myc by translocation appoarred in the early stage during the development of the bronchial epithelial cell line M. C-myc translocations were also found in bronchial epithelial cell line C45 and TR. The translocated chronosomes found In the three cell lines are similar:t(14:8) (q32;q23). In a lung adenocarcinoma cell line GLC-82,c-myc translocated to the long arm of chromosome 22. C-myc translocations were also found in 2/12 clinic NSCLC biopsies, with c-myc translocated to 14q or 22q respectively. We found overexpression of c-myc in the cases with c-myc translocation. Translocation as well as amplification contributed to the activation of c-myc oncogene.2. Loss of material from 2q was found in 3 bronchial epithelial cell lines, two lung cancer cell lines, and 3/7 clinic NSCLC biopies( one including bronchial epithelial cells adjacent to the tumor tissue). It indicates that loss of material from 2q is an important and early event in the development of NSCLC. One or more antioncogenes may locate on 2q. Loss of the gene(s) might be related to the carcinogenesis of bronchial epithelial cells.3. Chromosomal alterations related to 17q were found in 3 bronchial epithelial cell lines, two NSCLC cell lines, and 1 clinic NSCLC biopsy. In these cases, c-erbB-2 overexpression was detected. It hints that the alterations related to 17q may contribute to the c-erbB-2 activation. We have not found c-erbB-2 amplification in any case of our studies.4. Translocation related to 18q was found in the later stage of cell line N. It concurred with the resistance of the cells to PDD-induced apoptosis. Translocation related to 18q was also found in bronchial epithlial cell line Y and two cases of clinic NSCLC biopsies. In the cell lines we found the...