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Decreased expression of nucleoside diphosphate kinase α isoform, an nm23‐H2 gene homolog, is associated with metastatic potential of rat mammary‐adenocarcinoma cells
Author(s) -
Fukuda Mitsugu,
Ishii Akio,
Yasutomo Yoshiro,
Shimada Nobuko,
Ishikawa Naoshi,
Hanai Nobuo,
Nagata Naokazu,
Irimura Tatsuro,
Nicolson Garth L.,
Kimura Narimichi
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960208)65:4<531::aid-ijc23>3.0.co;2-b
Subject(s) - gene isoform , nucleoside diphosphate kinase , biology , transfection , microbiology and biotechnology , cell culture , northern blot , western blot , complementary dna , metastasis , cancer research , gene , gene expression , metastasis suppressor gene , cancer , biochemistry , genetics
The nm23 gene [encoding nucleoside diphosphate kinase (NDPK)] may act as a metastasis suppressor in certain tumor cells. We investigated the role of NDPK isoforms (α and β) in the metastatic processes, using rat mammary‐adenocarcinoma cell lines of poor (MTC) and high (MTLn3) spontaneous metastatic potential respectively. In these cell lines, as in most rat tissues, the α isoform (nm23‐H2 homolog) was more highly expressed than the β isoform (nm23‐H1 homolog) at the mRNA and protein levels. When examined by Northern‐ and Western‐blot analyses, expression of the 2 isoforms was reduced in highly metastatic MTLn3 cells compared with poorly metastatic MTC cells. The reduced expression was also associated with diminished NDPK‐enzyme activity in the cell extracts. Southern‐blot and RT‐PCR‐SSCP analyses suggested that the 2 genes were not grossly altered or mutated in their translation regions. MTLn3 cell clones transfected with NDPKα or NDPKβ cDNA were all tumorigenic when implanted into the mammary fat pad of syngeneic rats. Among those, only clones transfected with the NDPKα gene exhibited reduced lung metastasis in a spontaneous metastasis assay. © 1996 Wiley‐Liss, Inc.