Home LiteratureArticle Details
PMID: 9391102 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Replacement of Fhit in cancer cells suppresses tumorigenicity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 25 ·1997-12-09 ·Pages 13771-6

Siprashvili Z, Sozzi G, Barnes LD, McCue P, Robinson AK, Eryomin V, Sard L, Tagliabue E, Greco A, Fusetti L, Schwartz G, Pierotti MA, Croce CM, Huebner K

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.

MeSH Terms
Acid Anhydride Hydrolases Animals Cell Division/genetics,physiology Chromosome Fragile Sites Chromosome Fragility Chromosomes, Human, Pair 3/genetics Dinucleoside Phosphates/metabolism Genes, Tumor Suppressor Humans Mice Mice, Nude Mutation Neoplasm Proteins Neoplasm Transplantation Phenotype Phosphoric Diester Hydrolases/genetics,metabolism Proteins/genetics,metabolism Transfection Transplantation, Heterologous Tumor Cells, Cultured
Chemicals
Dinucleoside Phosphates Neoplasm Proteins Proteins fragile histidine triad protein Phosphoric Diester Hydrolases Acid Anhydride Hydrolases
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Siprashvili Z
Kimmel Cancer Center and Departments of Microbiology-Immunology and Pathology, Jefferson Medical College, Philadelphia, PA 19107, USA.
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
References (25)
25 references, click to expand
  1. Characteristics of a human cell line transformed by DNA from human adenovirus type 5.
    J Gen Virol. 1977 Jul;36(1):59-74 PMID: 886304
  2. The FHIT gene, a multiple tumor suppressor gene encompassing the carcinogen sensitive chromosome fragile site, FRA3B.
    Biochim Biophys Acta. 1997 Jun 7;1332(3):M65-70 PMID: 9196019
  3. Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx.
    Int J Cancer. 1980 Aug;26(2):127-32 PMID: 6259064
  4. Comparison of seven cell lines derived from human gastric carcinomas.
    Acta Pathol Jpn. 1986 Jan;36(1):65-83 PMID: 3962675
  5. Suppression of human colorectal carcinoma cell growth by wild-type p53.
    Science. 1990 Aug 24;249(4971):912-5 PMID: 2144057
  6. The HIT protein family: a new family of proteins present in prokaryotes, yeast and mammals.
    DNA Seq. 1992;3(3):177-9 PMID: 1472710
  7. Cloning of the Schizosaccharomyces pombe gene encoding diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) asymmetrical hydrolase: sequence similarity with the histidine triad (HIT) protein family.
    Biochem J. 1995 Dec 15;312 ( Pt 3):925-32 PMID: 8554540
  8. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers.
    Cell. 1996 Feb 23;84(4):587-97 PMID: 8598045
  9. The FHIT gene 3p14.2 is abnormal in lung cancer.
    Cell. 1996 Apr 5;85(1):17-26 PMID: 8620533
  10. Potential gastrointestinal tumor suppressor locus at the 3p14.2 FRA3B site identified by homozygous deletions in tumor cell lines.
    Cancer Res. 1996 Mar 1;56(5):978-83 PMID: 8640789
  11. A 350-kb cosmid contig in 3p14.2 that crosses the t(3;8) hereditary renal cell carcinoma translocation breakpoint and 17 aphidicolin-induced FRA3B breakpoints.
    Genomics. 1996 Jul 1;35(1):87-93 PMID: 8661108
  12. Direct cloning of DNA sequences from the common fragile site region at chromosome band 3p14.2.
    Genomics. 1996 Jul 1;35(1):109-17 PMID: 8661111
  13. The FHIT gene at 3p14.2 is abnormal in breast carcinomas.
    Cancer Res. 1996 Jul 15;56(14):3173-9 PMID: 8764101
  14. FHIT gene alterations in head and neck squamous cell carcinomas.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9770-5 PMID: 8790406
  15. Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5"'-P1,P3-triphosphate hydrolase.
    Biochemistry. 1996 Sep 10;35(36):11529-35 PMID: 8794732
  16. FRA3B extends over a broad region and contains a spontaneous HPV16 integration site: direct evidence for the coincidence of viral integration sites and fragile sites.
    Hum Mol Genet. 1996 Feb;5(2):187-95 PMID: 8824874
  17. Frequent abnormalities of FHIT, a candidate tumor suppressor gene, in head and neck cancer cell lines.
    Cancer Res. 1996 Nov 15;56(22):5128-31 PMID: 8912845
  18. Structure and expression of the human FHIT gene in normal and tumor cells.
    Cancer Res. 1997 Feb 1;57(3):504-12 PMID: 9012482
  19. Chromosome 3p14 homozygous deletions and sequence analysis of FRA3B.
    Hum Mol Genet. 1997 Feb;6(2):193-203 PMID: 9063739
  20. Positions of chromosome 3p14.2 fragile sites (FRA3B) within the FHIT gene.
    Cancer Res. 1997 Mar 15;57(6):1166-70 PMID: 9067288
  21. Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins.
    Nat Struct Biol. 1997 Mar;4(3):231-8 PMID: 9164465
  22. FHIT gene expression in human ovarian, endometrial, and cervical cancer cell lines.
    Cancer Res. 1997 Jun 1;57(11):2112-5 PMID: 9187105
  23. Association between cigarette smoking and FHIT gene alterations in lung cancer.
    Cancer Res. 1997 Jun 1;57(11):2121-3 PMID: 9187107
  24. FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations.
    Cancer Res. 1997 Jun 1;57(11):2256-67 PMID: 9187130
  25. Cell surface antigens of human renal cancer defined by autologous typing.
    J Exp Med. 1979 Sep 19;150(3):564-79 PMID: 479762
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.25.13771
Published
1997-12-09
Pages
13771-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC28382
Subset
IM
Grants
NCI NIH HHS · CA21124 · United States
NCI NIH HHS · CA51083 · United States
NCI NIH HHS · CA56336 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.25.13771 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2