The tumor suppressor gene WT1 inhibits ras-mediated transformation

X. N. Luo, J. C. Reddy, P. L. Yeyati, A. H. Idris, S. Hosono, D. A. Haber, J. D. Licht, G. F. Atweh

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated ras oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.

Original languageEnglish (US)
Pages (from-to)743-750
Number of pages8
JournalOncogene
Volume11
Issue number4
StatePublished - 1995

Fingerprint

Tumor Suppressor Genes
Wilms Tumor
Neoplasms
Contact Inhibition
ras Genes
Growth
Tumor Cell Line
Nude Mice
Agar
Carcinogenesis
Complementary DNA
Pediatrics
Phenotype
Mutation

Keywords

  • Ras-transformation
  • Tumor suppressors
  • WT1

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Luo, X. N., Reddy, J. C., Yeyati, P. L., Idris, A. H., Hosono, S., Haber, D. A., ... Atweh, G. F. (1995). The tumor suppressor gene WT1 inhibits ras-mediated transformation. Oncogene, 11(4), 743-750.

The tumor suppressor gene WT1 inhibits ras-mediated transformation. / Luo, X. N.; Reddy, J. C.; Yeyati, P. L.; Idris, A. H.; Hosono, S.; Haber, D. A.; Licht, J. D.; Atweh, G. F.

In: Oncogene, Vol. 11, No. 4, 1995, p. 743-750.

Research output: Contribution to journalArticle

Luo, XN, Reddy, JC, Yeyati, PL, Idris, AH, Hosono, S, Haber, DA, Licht, JD & Atweh, GF 1995, 'The tumor suppressor gene WT1 inhibits ras-mediated transformation', Oncogene, vol. 11, no. 4, pp. 743-750.
Luo XN, Reddy JC, Yeyati PL, Idris AH, Hosono S, Haber DA et al. The tumor suppressor gene WT1 inhibits ras-mediated transformation. Oncogene. 1995;11(4):743-750.
Luo, X. N. ; Reddy, J. C. ; Yeyati, P. L. ; Idris, A. H. ; Hosono, S. ; Haber, D. A. ; Licht, J. D. ; Atweh, G. F. / The tumor suppressor gene WT1 inhibits ras-mediated transformation. In: Oncogene. 1995 ; Vol. 11, No. 4. pp. 743-750.
@article{3aaef51b1efe4b96af10e364a78e29a6,
title = "The tumor suppressor gene WT1 inhibits ras-mediated transformation",
abstract = "Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated ras oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.",
keywords = "Ras-transformation, Tumor suppressors, WT1",
author = "Luo, {X. N.} and Reddy, {J. C.} and Yeyati, {P. L.} and Idris, {A. H.} and S. Hosono and Haber, {D. A.} and Licht, {J. D.} and Atweh, {G. F.}",
year = "1995",
language = "English (US)",
volume = "11",
pages = "743--750",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - The tumor suppressor gene WT1 inhibits ras-mediated transformation

AU - Luo, X. N.

AU - Reddy, J. C.

AU - Yeyati, P. L.

AU - Idris, A. H.

AU - Hosono, S.

AU - Haber, D. A.

AU - Licht, J. D.

AU - Atweh, G. F.

PY - 1995

Y1 - 1995

N2 - Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated ras oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.

AB - Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated ras oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.

KW - Ras-transformation

KW - Tumor suppressors

KW - WT1

UR - http://www.scopus.com/inward/record.url?scp=0029112359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029112359&partnerID=8YFLogxK

M3 - Article

C2 - 7651738

AN - SCOPUS:0029112359

VL - 11

SP - 743

EP - 750

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 4

ER -