Interaction of Nkx3.1 and p27kip1 in Prostate Tumor Initiation

Bernard Gary, Ricardo Azuero, Gayatree S. Mohanty, Walter C. Bell, Isam Eldin A Eltoum, Sarki A. Abdulkadir*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The homeodomain transcription factor Nkx3.1 and the cyclin-dependent kinase inhibitor p27kip1 have both been implicated in prostate tumor suppression. In addition, both of these molecules demonstrate haploinsufficiency for tumor suppression, in which loss of a single allele is sufficient to lead to the development of preneoplastic or neoplastic lesions. We have generated mice carrying compound mutant alleles of Nkx3.1 andp27 to explore the roles of these factors in prostate tumorigenesis. Our results indicate that Nkx3.1 and p27kip1 cooperate to suppress the proliferation of prostatic epithelial cells and the formation of preneoplastic lesions resembling prostatic intraepithelial neoplasia. Cooperativity was most evident with complete loss of at least one of the two genes because compound heterozygous mice exhibited a prostatic phenotype that was no more severe than that of single heterozygous mutants. Thus Nkx3.1 and p27kip1 regulate prostatic epithelial cell proliferation and tumor initiation by affecting both haploinsufficient and nonhaploinsufficient pathways.

Original languageEnglish (US)
Pages (from-to)1607-1614
Number of pages8
JournalAmerican Journal of Pathology
Volume164
Issue number5
DOIs
StatePublished - May 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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