Replacement of Fhit in cancer cells suppresses tumorigenicity
Replacement of Fhit in cancer cells suppresses tumorigenicity
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DOI：
10.1073/pnas.94.25.13771
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Huebner, K
中科院分区：
文献类型：
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作者：
Siprashvili, Z;Sozzi, G;Huebner, K
候选肿瘤抑制基因FHIT包括位于3p14.2的常见人类染色体脆性位点、遗传性肾癌易位断裂点和癌细胞纯合缺失。Fhit在体外水解二核苷酸5 '，5'-P-1，P-3-三磷酸，中心组氨酸的突变消除了水解酶活性。为了研究Fhit功能，将野生型和突变型FHIT基因转染到缺乏内源性Fhit的癌细胞系中。未观察到外源Fhit对培养物中生长的一致影响，但Fhit和水解酶“死"Fhit突变蛋白抑制裸鼠中的致瘤性，表明5 '，5”"-P-1，P-3-三磷酸水解不是肿瘤抑制所需的。
The candidate tumor suppressor gene, FHIT, encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal cancer translocation breakpoint, and cancer cell homozygous deletions. Fhit hydrolyzes dinucleotide 5',5'''-P-1,P-3-triphosphate in vitro and mutation of a central histidine abolishes hydrolase activity. To study Fhit function, wild-type and mutant FHIT genes were transfected into cancer cell lines that lacked endogenous Fhit. No consistent effect of exogenous Fhit on growth in culture was observed, but Fhit and hydrolase ''dead'' Fhit mutant proteins suppressed tumorigenicity in nude mice, indicating that 5',5'''-P-1,P-3-triphosphate hydrolysis is not required for tumor suppression.