Molecular cytogenetic alterations in the early stage at human bronchial epithelial cell carcinogenesis

Abstract

Lung carcinogenesis is a multi-step process involving activation of oncogenes and inactivation of tumor suppress genes. Many molecular and cytogenetic alterations occur in the early stages of carcinogenesis. We have developed an effective culture system for human bronchial epithelial cells and lung cancer cells. Four immortalized human bronchial epithelial cell lines were established by transfecting the epithelial cells with plasmid DNA containing the early region of SV40. Some molecular and cytogenetic alterations, such as 3p-, 2q-, 9p-, c-myc translocation t(8;14) (q23; q32), were found in one immortalized bronchial epithelial cell line M when approaching malignant transformation. An increase in cell proliferation and decrease of apoptosis were noted in the late passages of the immortalized cell line M. Some molecular cytogenetic alterations were also observed in human primary non-small cell lung cancers. Molecular cytogenetic alterations during the early stage of carcinogenesis of human bronchial epithelial cells may be useful as biomarkers for both diagnosis and intermediate endpoint of chemoprevention of lung cancer. J. Cell. Biochem. Suppls. 28/29:74-80. 1998 Wiley-Liss, Inc. 1998 Wiley-Liss, Inc.*CFE: colony forming efficiency; PD/D: per doubling/day; EGF: epidermal growth factor; MSFM-EGF: deprivation of EGF from MSFM. CFE% and PD/D between M(p16) and M(p71) P Ͻ 0.01; CFE% and PD/D of M(p16) between MSFM and MSFM-EGF, P Ͻ 0.01.

Cathepsin D Is Secreted from M-BE Cells: Its Potential Role as a Biomarker of Lung Cancer

“…10 M-BE is an immortalized human bronchial epithelial cell line by transfection of noncancerous individual bronchial epithelial cells with plasmids containing SV40 early region genes. 10,11 In contrast to M-BE cells at early passage (P16), their late passage (P71) displayed fast proliferation, independent of EGF regulation and resistant to serum-induced differentiation. 10,11 Many cytogenetic events, such as translocation of 18q and activation of c-erbB-2, bcl2, and c-myc, also changed toward abnormity in late passage M-BE cells.…”

“…10,11 In contrast to M-BE cells at early passage (P16), their late passage (P71) displayed fast proliferation, independent of EGF regulation and resistant to serum-induced differentiation. 10,11 Many cytogenetic events, such as translocation of 18q and activation of c-erbB-2, bcl2, and c-myc, also changed toward abnormity in late passage M-BE cells. 10 However, no tumor formation was observed when the high-passage M-BE cells were injected into nude mice, even though these cells reconstructed in rat bronchial trachea were able to generate hyperplasia and squamous meteplasia of epithelial tissue.…”

Squamous cell lung cancer: genomic evolution and personalized therapy

“…31,32 Chromosomal gains and losses in chromosomes 1q, 3p, 8p, 8q, 12q, and 17q have been shown previously in CIS using comparative genomic hybridization. [32][33][34] LOH studies have shown a wide spectrum of changes in several loci, especially in 3p. This highlights that a number of possible TSG are altered in the initial process of bronchial carcinogenesis.…”

Treatment of Carcinogenesis

“…Furthermore, in addition to using development of primary or secondary cancer as end points in chemoprevention studies, potential biomarkers are known. Intermediate markers of lung carcinogenesis include histologic lesions such as bronchial metaplasia and dysplasia (309)(310)(311) and genetic abnormalities such as loss of heterozygosity at chromosomes 3p and 9p (312)(313)(314). Other biomarkers of lung carcinogenesis being evaluated include mutations in p53, the TSG (315); the oncogene ras (316)(317)(318); epigenetic abnormalities such as hypermethylation of the promoter region of receptor molecules, including EGFR (319,320); the retinoid receptors RAR and RXR (321,322); and enzymes that regulate synthesis of prostaglandins (323).…”