Molecular mechanisms possibly affecting WT1 function in human ovarian tumors
- PMID: 7910152
- DOI: 10.1002/ijc.2910570413
Molecular mechanisms possibly affecting WT1 function in human ovarian tumors
Abstract
The frequent allelic deletions observed on the short arm of chromosome 11 in ovarian tumors suggest that the WT1 gene, a proposed tumor-suppressor gene located on chromosome 11p13 and expressed in the human fetal genitourinary system, may contribute to the development of ovarian neoplasms. Structural and sequence analysis of the entire coding portions of the WT1 gene did not reveal any abnormalities in the 20 ovarian tumor specimens (13 of which showed 11p13 allelic deletions) and 5 cell lines which we analyzed. These findings invalidate the hypothesis that the WT1 gene functions as a classical tumor-suppressor gene in ovarian tumorigenesis and suggest that a different recessive oncogene may be "exposed" by the observed 11p13 allelic deletions. Expression analysis showed that the WT1 gene was transcriptionally active in all the tumors tested, but considerable variations in the mRNA levels were found. This apparent variability, which should be confirmed at the cellular level in the tumor specimens, was also observed in the ovarian tumor-cell lines. Finally, WT1 expression data were evaluated in conjunction with immunohistochemical data on p53. The possible functional effects of altered WT1 mRNA expression in ovarian tumors are discussed, taking into account the potential WT1/p53 protein interaction.
Similar articles
-
Constitutional and somatic mutations in the WT1 gene in Wilms' tumor patients.Int J Cancer. 1995 Nov 15;63(4):516-22. doi: 10.1002/ijc.2910630410. Int J Cancer. 1995. PMID: 7591260
-
Identification of the cellular protein encoded by the human Wilms' tumor (WT1) gene.Oncogene. 1992 Dec;7(12):2545-8. Oncogene. 1992. PMID: 1334252
-
Analysis of the 11p13 Wilms' tumor suppressor gene (WT1) in ovarian tumors.Cancer Invest. 1993;11(4):393-9. doi: 10.3109/07357909309018871. Cancer Invest. 1993. PMID: 8324644
-
The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor.FASEB J. 1993 Jul;7(10):896-903. FASEB J. 1993. PMID: 8393820 Review.
-
Wilms tumor and the WT1 gene.Exp Cell Res. 2001 Mar 10;264(1):74-99. doi: 10.1006/excr.2000.5131. Exp Cell Res. 2001. PMID: 11237525 Review.
Cited by
-
The genetic analysis of ovarian cancer.Br J Cancer. 1995 Sep;72(3):521-7. doi: 10.1038/bjc.1995.367. Br J Cancer. 1995. PMID: 7669555 Free PMC article. Review. No abstract available.
-
Wilms tumor gene (WT1) expression as a panleukemic marker.Int J Hematol. 2002 Aug;76(2):103-9. doi: 10.1007/BF02982571. Int J Hematol. 2002. PMID: 12215007 Review.
-
Wilms' tumor 1 susceptibility (WT1) gene products are selectively expressed in malignant mesothelioma.Am J Pathol. 1995 Feb;146(2):344-56. Am J Pathol. 1995. PMID: 7856747 Free PMC article.
-
Cancer immunotherapy targeting WT1 protein.Int J Hematol. 2002 Aug;76(2):127-32. doi: 10.1007/BF02982574. Int J Hematol. 2002. PMID: 12215010 Review.
-
Chromosome 11 allele imbalance and clinicopathological correlates in ovarian tumours.Br J Cancer. 1995 Aug;72(2):367-75. doi: 10.1038/bjc.1995.340. Br J Cancer. 1995. PMID: 7640220 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous