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

doi:10.1073/pnas.94.25.13771

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

Pathology

Thomas Jefferson University
Fondazione IRCCS Istituto Nazionale dei Tumori
University of Texas Health Science Center at San Antonio
Memorial Sloan-Kettering Cancer Center

Research output: Contribution to journal › Article › peer-review

367 Scopus citations

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.

Original language	English
Pages (from-to)	13771-13776
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	94
Issue number	25
DOIs	https://doi.org/10.1073/pnas.94.25.13771
State	Published - Dec 9 1997

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Acid Anhydride Hydrolases
Animals
Cell Division/genetics
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
Proteins/genetics
Transfection
Transplantation, Heterologous
Tumor Cells, Cultured

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10.1073/pnas.94.25.13771

Cite this

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. (1997). Replacement of Fhit in cancer cells suppresses tumorigenicity. Proceedings of the National Academy of Sciences of the United States of America, 94(25), 13771-13776. https://doi.org/10.1073/pnas.94.25.13771

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title = "Replacement of Fhit in cancer cells suppresses tumorigenicity",

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.",

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

year = "1997",

month = dec,

day = "9",

doi = "10.1073/pnas.94.25.13771",

language = "English",

volume = "94",

pages = "13771--13776",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "25",

}

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

TY - JOUR

T1 - Replacement of Fhit in cancer cells suppresses tumorigenicity

AU - Siprashvili, Zurab

AU - Sozzi, Gabriella

AU - Barnes, Larry D.

AU - Mccue, Peter

AU - Robinson, Angela K.

AU - Eryomin, Vladimir

AU - Sard, Laura

AU - Tagliabue, Elda

AU - Greco, Angela

AU - Fusetti, Lisa

AU - Schwartz, Gary

AU - Pierotti, Marco A.

AU - Croce, Carlo M.

AU - Huebner, Kay

PY - 1997/12/9

Y1 - 1997/12/9

N2 - 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.

AB - 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.

KW - Acid Anhydride Hydrolases

KW - Animals

KW - Cell Division/genetics

KW - Chromosome Fragile Sites

KW - Chromosome Fragility

KW - Chromosomes, Human, Pair 3/genetics

KW - Dinucleoside Phosphates/metabolism

KW - Genes, Tumor Suppressor

KW - Humans

KW - Mice

KW - Mice, Nude

KW - Mutation

KW - Neoplasm Proteins

KW - Neoplasm Transplantation

KW - Phenotype

KW - Phosphoric Diester Hydrolases/genetics

KW - Proteins/genetics

KW - Transfection

KW - Transplantation, Heterologous

KW - Tumor Cells, Cultured

UR - https://www.scopus.com/pages/publications/13144262880

U2 - 10.1073/pnas.94.25.13771

DO - 10.1073/pnas.94.25.13771

M3 - Article

C2 - 9391102

AN - SCOPUS:13144262880

SN - 0027-8424

VL - 94

SP - 13771

EP - 13776

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 25

ER -

Replacement of Fhit in cancer cells suppresses tumorigenicity

Abstract

UN SDGs

Keywords

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