Metastasis suppressors Nm23H1 and Nm23H2 differentially regulate neoplastic transformation and tumorigenesis.
Nm23H1 and H2 are prototypical metastasis suppressors with diverse functions, but recent studies suggest that they may also regulate tumorigenesis. Here, we employed both cellular and in vivo assays to examine the effect of Nm23H1 and H2 on tumorigenesis induced by oncogenic Ras and/or p53 deficiency. Co-expression of Nm23H1 but not H2 in NIH3T3 cells effectively suppressed neoplastic transformation and tumorigenesis induced by the oncogenic H-Ras G12V mutant. Overexpression of Nm23H1 but not H2 also inhibited tumorigenesis by human cervical cancer HeLa cells with p53 deficiency. However, in human non-small-cell lung carcinoma H1299 cells harboring N-Ras Q61K oncogenic mutation and p53 deletion, overexpression of Nm23H1 did not affect tumorigenesis in nude mice assays, while overexpression of Nm23H2 enhanced tumor growth with elevated expression of the c-Myc proto-oncogene. Collectively, these results suggest that Nm23H1 and H2 have differential abilities to modulate tumorigenesis.
Division of Life Sciences, Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Yao
Y
Tong
Division of Life Sciences, Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Lisa Y
LY
Yung
Division of Life Sciences, Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong; State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong. Electronic address: boyung@ust.hk.
Yung H
YH
Wong
D000818:Animals; D063646:Carcinogenesis; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D000090063:Proto-Oncogene Mas; D014162:Transfection
C000715470:MAS1 protein, human; D054778:NM23 Nucleoside Diphosphate Kinases; D000090063:Proto-Oncogene Mas; C517938:NME1 protein, human; C517940:NME2 protein, human
NDPK; Neoplastic transformation; Nm23; Ras; Tumorigenesis