A novel mitochondrial C1-tetrahydrofolate synthetase is upregulated in human colon adenocarcinoma.
To seek the genes involved in the development of colorectal cancer, we analyzed the microarray gene expression profiles of human normal and cancerous colon tissues using the BioExpress database platform. Through the analysis we found one gene named DKFZp586G1517 that was upregulated in colon adenocarcinomas. The full-length cDNA of the DKFZp586G1517 cloned by polymerase chain reaction (PCR) encodes a protein with 978 amino acids, which is homologous to the human cytosolic C(1)-tetrahydrofolate synthetase and contains a mitochondrial target signal at N-terminus. The gene product expressed in 293 cells was localized in mitochondria and processed at the predicted signal cleavage site, supporting the idea that DKFZp586G1517 is a novel mitochondrial C(1)-tetrahydrofolate synthetase (mtC(1)-THFS). The overexpression of mtC(1)-THFS in 293 cells stimulated the colony formation. These results suggest that mtC(1)-THFS may participate in the progression of colorectal cancer by conferring growth advantage and could be a new molecular target for cancer therapy.
Sugiura
Takeyuki
T
Discovery Research Laboratory, Tokyo R&D Center, Daiichi Pharmaceutical Co. Ltd., 16-13, Kitakasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan. sugiuy79@daiichipharm.co.jp
Nagano
Yuki
Y
Inoue
Tatsuya
T
Hirotani
Kenji
K
D000230:Adenocarcinoma / Q000201:enzymology*; D000595:Amino Acid Sequence; D000619:Aminohydrolases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000201:enzymology*; D018076:DNA, Complementary / Q000235:genetics; D005574:Formate-Tetrahydrofolate Ligase / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D015854:Up-Regulation
D018076:DNA, Complementary; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; C021836:formyl-methenyl-methylenetetrahydrofolate synthetase; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000619:Aminohydrolases; D005574:Formate-Tetrahydrofolate Ligase