Identification of AXUD1, a novel human gene induced by AXIN1 and its reduced expression in human carcinomas of the lung, liver, colon and kidney.
Axin, an important regulator of beta-catenin, is frequently mutated in human hepatocellular carcinomas (HCCs), and transduction of the wild-type Axin gene (AXIN1) induces apoptosis in HCC cells as well as in colon cancer cells. To investigate the detailed biological function of Axin, we searched on a cDNA microarray for genes whose expression was altered by transfer of wild-type AXIN1 into colon-cancer cell line LoVo. Among the genes showing altered expression, we focused on one, termed AXUD1 (AXIN1 up-regulated), that revealed enhanced expression in response to exogenously expressed AXIN1 but not to LacZ, a control gene. The AXUD1 gene consists of five exons and encodes a transcript with an open reading frame of 1767 bp. A 3.2-kb transcript of AXUD1 was expressed in all human tissues examined, most abundantly in lung, placenta, skeletal muscle, pancreas and leukocyte. By radiation-hybrid mapping we assigned its chromosomal location at 3p22, a region where frequent loss of heterozygosity has been reported in lung, renal, prostate, breast and cervical cancers. AXUD1 was frequently down-regulated in lung, kidney, liver and colon cancers compared with their corresponding normal tissues, suggesting that AXUD1 may have a tumor-suppressor function in those organs.
Ishiguro
H
H
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Tsunoda
T
T
Tanaka
T
T
Fujii
Y
Y
Nakamura
Y
Y
Furukawa
Y
Y
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D060466:Axin Protein; D001483:Base Sequence; D019556:COS Cells; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012097:Repressor Proteins; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C555451:AXIN1 protein, human; D051017:Apoptosis Regulatory Proteins; D060466:Axin Protein; C434543:CSRNP1 protein, human; D011506:Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins