This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moreno-Bueno, G. Articles by Palacios, J. Search for Related Content PubMed PubMed Citation Articles by Moreno-Bueno, G. Articles by Palacios, J.

Inactivation of the Candidate Tumor Suppressor Par-4 in Endometrial Cancer

¹ Breast and Gynecological Cancer Group, ² Tumor Suppression Group, Spanish National Cancer Center (CNIO); ³ Department of Pathology, University Hospital "La Paz"; and ⁴ Center of Molecular Biology "Severo Ochoa" (CSIC-UAM), Madrid, Spain

Requests for reprints: Manuel Serrano or Jose Palacios, Spanish National Cancer Center (CNIO), 3 Melchor Fernandez Almagro Street, Madrid E-28029, Spain. Phone: 34-91-732-8032; Fax: 34-91-732-8028; E-mail: mserrano{at}cnio.es or jose.palacios.sspa{at}juntadeandalucia.es.

Recently, it has been shown that mice deficient in the proapoptotic protein prostate apoptosis response 4 (Par-4) are specifically prone to develop endometrial carcinomas. Based on this, we have examined here the possible role of Par-4 as a tumor suppressor gene in human endometrial cancer. Using cDNA arrays, quantitative reverse transcription-PCR, and immunohistochemistry, we detected Par-4 down-regulation in 40% of endometrial carcinomas. This alteration was not associated with phosphatase and tensin homologue (PTEN), K-RAS, or ß-catenin mutations, but was more frequent among tumors showing microsatellite instability (MSI) or among tumors that were estrogen receptor positive. Mutational analysis of the complete coding sequence of Par-4 in endometrial cancer cell lines (n = 6) and carcinomas (n = 69) detected a mutation in a single carcinoma, which was localized in exon 3 [Arg (CGA) 189 (TGA) Stop]. Interestingly, Par-4 promoter hypermethylation was detected in 32% of the tumors in association with low levels of Par-4 protein and was more common in MSI-positive carcinomas. Par-4 promoter hypermethylation and silencing was also detected in endometrial cancer cell lines SKUT1B and AN3CA, and reexpression was achieved by treatment with the demethylating agent 5'-aza-2'-deoxycytidine. Together, these data show that Par-4 is a relevant tumor suppressor gene in human endometrial carcinogenesis. [Cancer Res 2007;67(5):1927–34]

This article has been cited by other articles:

				A. Goswami, S. Qiu, T. S. Dexheimer, P. Ranganathan, R. Burikhanov, Y. Pommier, and V. M. Rangnekar Par-4 Binds to Topoisomerase 1 and Attenuates Its DNA Relaxation Activity Cancer Res., August 1, 2008; 68(15): 6190 - 6198. [Abstract] [Full Text] [PDF]

				Y. Zhao, R. Burikhanov, S. Qiu, S. M. Lele, C. D. Jennings, S. Bondada, B. Spear, and V. M. Rangnekar Cancer Resistance in Transgenic Mice Expressing the SAC Module of Par-4 Cancer Res., October 1, 2007; 67(19): 9276 - 9285. [Abstract] [Full Text] [PDF]