癌细胞中Fhit的替代抑制肿瘤发生。
Replacement of Fhit in cancer cells suppresses tumorigenicity.
作者信息
Siprashvili Z, Sozzi G, Barnes L D, McCue P, Robinson A K, Eryomin V, Sard L, Tagliabue E, Greco A, Fusetti L, Schwartz G, Pierotti M A, Croce C M, Huebner K
机构信息
Kimmel Cancer Center and Departments of Microbiology-Immunology and Pathology, Jefferson Medical College, Philadelphia, PA 19107, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13771-6. doi: 10.1073/pnas.94.25.13771.
Abstract
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"'-P1,P3-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"'-P1, P3-triphosphate hydrolysis is not required for tumor suppression.
摘要
候选抑癌基因FHIT包含人类常见的位于3p14.2的染色体脆性位点、遗传性肾癌易位断点以及癌细胞纯合缺失区域。Fhit在体外可水解二核苷酸5',5"'-P1,P3-三磷酸，而一个中心组氨酸的突变会消除水解酶活性。为研究Fhit的功能，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。未观察到外源性Fhit对细胞培养生长有一致的影响，但Fhit和水解酶“失活”的Fhit突变蛋白可抑制裸鼠的肿瘤发生，这表明肿瘤抑制并不需要5',5"'-P1, P3-三磷酸水解。
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