Replacement of Fhit in cancer cells suppresses tumorigenicity

Zurab Siprashvili, Gabriella Sozzi, Larry D. Barnes, Peter Mccue, Angela K. Robinson, Vladimir Eryomin, Laura Sard, Elda Tagliabue, Angela Greco, Lisa Fusetti, Gary Schwartz, Marco A. Pierotti, Carlo M. Croce, Kay Huebner

Research output: Contribution to journalArticle

344 Citations (Scopus)

Abstract

The candidate tumor suppressor gene, FHIT, encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal caller translocation breakpoint, and cancer cell homozygous deletions. Fhit hydrolyzes dinucleotide 5',5m-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',5m-P1,P3-triphosphate hydrolysis is not required for tumor suppression.

Original languageEnglish
Pages (from-to)13771-13776
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number25
DOIs
Publication statusPublished - Dec 9 1997

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Hydrolases
Neoplasms
Mutant Proteins
Tumor Suppressor Genes
Histidine
Nude Mice
Hydrolysis
Kidney
Cell Line
Mutation
Growth
Genes
triphosphoric acid
In Vitro Techniques

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Replacement of Fhit in cancer cells suppresses tumorigenicity. / Siprashvili, Zurab; Sozzi, Gabriella; Barnes, Larry D.; Mccue, Peter; Robinson, Angela K.; Eryomin, Vladimir; Sard, Laura; Tagliabue, Elda; Greco, Angela; Fusetti, Lisa; Schwartz, Gary; Pierotti, Marco A.; Croce, Carlo M.; Huebner, Kay.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 25, 09.12.1997, p. 13771-13776.

Research output: Contribution to journalArticle

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 1997, '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, pp. 13771-13776. https://doi.org/10.1073/pnas.94.25.13771
Siprashvili, Zurab ; Sozzi, Gabriella ; Barnes, Larry D. ; Mccue, Peter ; Robinson, Angela K. ; Eryomin, Vladimir ; Sard, Laura ; Tagliabue, Elda ; Greco, Angela ; Fusetti, Lisa ; Schwartz, Gary ; Pierotti, Marco A. ; Croce, Carlo M. ; Huebner, Kay. / Replacement of Fhit in cancer cells suppresses tumorigenicity. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 25. pp. 13771-13776.
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