ABSTRACT
The kinetics and subcellular localization of nm23-M1 and -M2 was reported in in vivo regenerating mouse liver cells after partial hepatectomy (Lee et al. 1997a). On the human nm23-H2 transgenic mice, the kinetics of murine types of nm23 and mitotic index were very similar to results from ordinary mice B6, whereas the kinetics of human type of nm23 was responded strongly and shortly in early phase of regeneration. In subcellular study, all fractions of nm23-H2 protein at 6hr after partial hepatectomy were increased to very high level and decreased soon day 1. These studies suggest that exogenous DNA sequence nm23-H2 expressed immediately in early phase of hepatocyte regeneration, and in short term duration comparing with native murine type of nm23. This analysis might include that another cellular cofactor(s) is(are) necessary for human type nm23 expression in regenerating mouse hepatocyte in playing a role as a transcription factor, or that is not associated with any cellular cofactors in organ crisis.
Subject(s)
Animals , Humans , Mice , Base Sequence , Hepatectomy , Hepatocytes , Kinetics , Liver , Mice, Transgenic , Mitotic Index , Phosphotransferases , Regeneration , Transcription Factors , Up-RegulationABSTRACT
Since Steeg, et al.(1988) identified NM23/NDP kinase as non -metastasis gene, other multiple functions of have reported. One of them, Postel, et al.(1993) suggested that transcription factor PuF, being encoded by NM23 -H2/NDP kinase gene, interacts with nuclease hypersensitive element located upstream of the c -myc gene. C -myc amplification and activation can be present in squamous cell carcinoma of the head and neck as well as in an increased metastatic propensity for individual tumor. To clarify the role of NM23/NDP kinase on c -myc expression, comparison of these two gene expressions in cell lines was done. No direct correlation of expression kinetics was found. A plasmid containing human c -myc fragment was cloned upstream of chloramphenicol acetyltransferase (CAT) gene. When murine melanoma cell line was cotransfected with a murine NM23 -M2 including expression vector and c -myc CAT, CAT activity was elevated, while no change of CAT activity was found in the cotransfectant of human NM23 -H2 and c -myc CAT. Data suggest that murine NM23 -M2 gene transactivates c -myc gene indirectly with a cellular factor in murine cell line which dose not work with human NM23 -H2 gene. Additionally, we found same kinetics of NM23 -H2/NDP kinase and c -myc expression change correlated with proliferation of PLC/PRF/5 which was induced by HGF.
Subject(s)
Animals , Cats , Humans , Carcinoma, Squamous Cell , Cell Line , Chloramphenicol O-Acetyltransferase , Clone Cells , Gene Expression , Head , Kinetics , Melanoma , Neck , Phosphotransferases , Plasmids , Transcription Factors , Transcriptional ActivationABSTRACT
Two isotypes of nm23 gene have been reported as multifunctional genes as well as CD44 gene. In tumor, both of genes, one isotype of human nm23, nm23-H1 and splice variants of surface glycoprotein CD44[CD44 v8-10], are correlated with tumor growth and metatastic potential[Keim et al., 1992 ; Dall et al., 1995]. However, the correlation of expression between these genes in tumor was not reported. In this immunohistochemical study on skin cancers, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma, we intended to clarify the differences of expression on the basis of origins of skin tumors, basal cell, prickle cell, melanin producing cell, and compare the alterations of expressions between two genes in each tumor, respectively. The conclusion of this comparison is that relative parallel alteration in expressions between nm23-H1/NDP kinase and CD44 v8-10 was observed in basal cell carcinoma and malignant melanoma with inverse relation in differentiation. In squamous carcinoma, the expressions of two genes were much associated with differentiation. On the periphery of tumor, very low level of nm23-H1 protein and high level of CD44 v8-10 protein were detected.