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Cell Rep. 2014 Mar 27;6(6):1000-1007. doi: 10.1016/j.celrep.2014.02.023. Epub 2014 Mar 13.

miR-34 cooperates with p53 in suppression of prostate cancer by joint regulation of stem cell compartment.

Author information

1
Department of Biomedical Sciences and Cornell Stem Cell Program, Cornell University, Ithaca, NY 14853, USA.
2
Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität, 80337 Munich, Germany.
3
Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität, 80337 Munich, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
4
Department of Biomedical Sciences and Cornell Stem Cell Program, Cornell University, Ithaca, NY 14853, USA. Electronic address: an58@cornell.edu.

Erratum in

  • Cell Rep. 2015 Sep 29;12(12):2181.

Abstract

The miR-34 family was originally found to be a direct target of p53 and is a group of putative tumor suppressors. Surprisingly, mice lacking all mir-34 genes show no increase in cancer formation by 18 months of age, hence placing the physiological relevance of previous studies in doubt. Here, we report that mice with prostate epithelium-specific inactivation of mir-34 and p53 show expansion of the prostate stem cell compartment and develop early invasive adenocarcinomas and high-grade prostatic intraepithelial neoplasia, whereas no such lesions are observed after inactivation of either the mir-34 or p53 genes alone by 15 months of age. Consistently, combined deficiency of p53 and miR-34 leads to acceleration of MET-dependent growth, self-renewal, and motility of prostate stem/progenitor cells. Our study provides direct genetic evidence that mir-34 genes are bona fide tumor suppressors and identifies joint control of MET expression by p53 and miR-34 as a key component of prostate stem cell compartment regulation, aberrations in which may lead to cancer.

PMID:
24630988
PMCID:
PMC3988786
DOI:
10.1016/j.celrep.2014.02.023
[Indexed for MEDLINE]
Free PMC Article

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