Isolation of a novel gene, TSP50, by a hypomethylated DNA fragment in human breast cancer.
A novel gene, testes-specific protease 50 (TSP50), was isolated from a human testes cDNA library by using a genomic DNA probe, BR50. BR50 was isolated by a modified representational difference analysis (RDA) technique due to its hypomethylated feature in a breast cancer biopsy. This altered DNA methylation status was also detected by BR50 in other breast and some ovarian cancer tissues. The TSP50 gene product is a homologue to several human proteases, which indicates that it may encode a protease-like protein. Northern analysis of 16 different types of normal human tissues suggests that TSP50 was highly and specifically expressed in human testes, which indicates that it might possess a unique biological function(s) in that organ. Methylation status analysis in normal human testes and other tissues showed a correlation between DNA methylation and gene expression. Most importantly, reverse transcription-PCR analysis of 18 paired breast cancer tissues found that in 28% of the cancer samples, the TSP50 gene was differentially expressed. The possibility that TSP50 may be an oncogene is presently under investigation.
Molecular Oncology, Hematology/Oncology Medicine, North Shore-Long Island Jewish Health System, New York University School of Medicine, Manhasset 11030, USA.
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De Risi
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Broome
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Lovecchio
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D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D002403:Cathepsins / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003546:Cysteine Endopeptidases / Q000235:genetics*; D019175:DNA Methylation; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015723:Gene Library; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics*; D010053:Ovary / Q000201:enzymology; D016133:Polymerase Chain Reaction; D012016:Reference Values; D013737:Testis / Q000201:enzymology
D015342:DNA Probes; D004273:DNA, Neoplasm; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C117627:CTSV protein, human