Activation of the met oncogene in the human MNNG-HOS cell line involves a chromosomal rearrangement

Abstract

In this study it is demonstrated that the activated met gene, which was originally detected in the MNNG-HOS chemically transformed human cell line, is a chimeric gene formed by the joining together of two distinct regions of DNA. Rearrangement of cellular DNA in MNNG-HOS cells was demonstrated by Southern analyses, which showed that the MNNG-HOS cell line contained unique met-related DNA fragments that were not detected in the parental cell line, HOS. Chromosomal localization using a series of rodent-human hybrid cell lines showed that the 5' end of the activated met gene is derived from human chromosome 1, in contrast to the 3' end of met which has been previously localized to human chromosome 7. The chimeric gene is transcribed to produce a 5-kb mRNA that is encoded both by regions of the gene derived from chromosome 1 and by regions of the gene derived from chromosome 7. Karyotype analysis of HOS and MNNG-HOS cells has identified several marker chromosomes that involve translocations of chromosomes 1 and 7. The possible location of the activated met locus within these rearranged chromosomes is discussed.

Horizontal gene transfers and cell fusions in microbiology, immunology and oncology (Review)

“…It acts as an oncogene in the N-methyl-N'-nitro-N-nitrosoguanidine-(MNNG)-transformed human osteosarcoma (HOS) cell line (231)(232)(233). The MET oncoprotein is the receptor for hepatocyte growth factor/scatter factor (HGF/SF) ligands (213) (see above).…”

The role of non-ras transforming genes in chemical carcinogenesis.

“…1 (13,14). This chimeric gene is transcribed to produce a unique 5.0-kb hybrid tpr-met mRNA that is in turn translated to form a 60-to 65-kDa fusion protein in which the protein tyrosine kinase domain of met is fused to the amino-terminal region of the trp protein (13,14,29,33).…”

“…For example, H-ras is activated in N-methyl-N-nitrosourea (MNU)-induced rat mammary tumors and in dimethylbenz[a]anthracene (DMBA)-initiated mouse skin papillomas and carcinomas, while both N-ras and K-ras are activated in thymomas that arise in MNU-treated RF/AKR mice (7)(8)(9)(10)(11)(12). However, genes that are unrelated to ras are also frequently detected, and in a minority of cases (e.g., for met and neu), the mechanism of gene activation of these non-ras genes has been examined in detail (13)(14)(15)(16). Since the role of ras gene activation in chemical carcinogenesis has been adequately discussed elsewhere (17)(18)(19), this review will deal entirely with the non-ras genes that are activated in chemically induced tumors and chemically transformed cell lines.…”

RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met-mediated tumorigenesis

“…16 Two leucine zippers in the Tpr moiety cause constitutive dimerization and sustained activation of the Met kinase domain. 17 The Tpr-Met translocation arose in a human osteosarcoma cell line after treatment with the chemical carcinogen N-methyl-N 0 -nitro-N-nitrosoguanidine (MNNG).…”

“…17 The Tpr-Met translocation arose in a human osteosarcoma cell line after treatment with the chemical carcinogen N-methyl-N 0 -nitro-N-nitrosoguanidine (MNNG). 16 It has been shown that MNNG causes gastric cancer in monkeys. 18 Although not common in human tumors, Tpr-Met has been reported in gastric carcinomas.…”