Molecular cloning and characterization of the tumor transforming gene (TUTR1): a novel gene in human tumorigenesis.
We cloned and sequenced the cDNA of a potent tumor transforming gene (TUTR1) from human testis and determined its primary structure. The TUTR1 cDNA is composed of 656 nucleotides and encodes a novel protein of 202 amino acids. The predicted TUTR1 protein is extremely hydrophilic and contains two proline-rich motifs at its C-terminus. Northern blot analysis of the mRNA from various human tissues and tumors revealed that TUTR1 mRNA is highly expressed in tumors of the pituitary gland, adrenal gland, ovary, endometrium, liver, uterus, and kidney as well as in cell lines derived from tumors of the pituitary, breast, endometrium, and ovary. With the exception of the testis, the levels of TUTR1 mRNA were either very low or undetectable in normal human tissues. Overexpression of TUTR1 in mouse fibroblasts (NIH 3T3) cells resulted in an increase in cell proliferation, induced cellular transformation in vitro, and promoted tumor formation in nude mice. These results suggest that TUTR1 is a novel and potent transforming gene, which may be involved in tumorigenesis in numerous different human tumors.
Kakar
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Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama, USA. Kakar@phybio.bhs.uab.edu
Jennes
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003001:Cloning, Molecular; D020224:Expressed Sequence Tags; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000473:pathology; D009928:Organ Specificity; D010750:Phosphoproteins; D011392:Proline / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D064249:Securin; D013737:Testis / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D011392:Proline