This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Yang, Q. Articles by Kakudo, K. Search for Related Content PubMed PubMed Citation Articles by Yang, Q. Articles by Kakudo, K.

(American Journal of Pathology. 2001;158:299-303.)
© 2001 American Society for Investigative Pathology

Regular Articles

Biallelic Inactivation of Retinoic Acid Receptor ß2 Gene by Epigenetic Change in Breast Cancer

Qifeng Yang^*, Ichiro Mori^*, Liang Shan^*, Misa Nakamura^*, Yasushi Nakamura^*, Hirotoshi Utsunomiya^*, Goro Yoshimura, Takaomi Suzuma, Takeshi Tamaki, Teiji Umemura, Takeo Sakurai and Kennichi Kakudo^*

From the Second Department of Pathology^*
and Department of Surgery,
Wakayama Medical College, Wakayama, Japan; and the Laboratory of Experimental Carcinogenesis,
National Cancer Institute, Bethesda, Maryland

A growing body of evidence supports the hypotheses that retinoic acid receptor ß2 (RAR ß2) is a tumor suppressor gene. Although the loss of RAR ß2 expression has been reported in many malignant tumors, including breast cancer, the molecular mechanism is still poorly understood. We hypothesized that loss of RAR ß2 activity could result from multiple factors, including epigenetic modification and loss of heterozygosity (LOH). Using methylation-specific polymerase chain reaction and LOH analysis, we found that biallelic inactivation via epigenetic changes of both maternal and paternal alleles, or epigenetic modification of one allele combined with genetic loss of the remaining allele, could completely suppress RAR ß2 expression in breast cancer. Thus, it is possible that substantial numbers of human cancers arise through suppressor gene silencing via epigenetic mechanisms that inactivate both alleles. Because of this, chromatin-remodeling drugs may provide a novel strategy for cancer prevention and treatment.

This article has been cited by other articles:

				M. O. Hoque, O. Topaloglu, S. Begum, R. Henrique, E. Rosenbaum, W. Van Criekinge, W. H. Westra, and D. Sidransky Quantitative Methylation-Specific Polymerase Chain Reaction Gene Patterns in Urine Sediment Distinguish Prostate Cancer Patients From Control Subjects J. Clin. Oncol., September 20, 2005; 23(27): 6569 - 6575. [Abstract] [Full Text] [PDF]

				N. P. Mongan and L. J. Gudas Valproic acid, in combination with all-trans retinoic acid and 5-aza-2'-deoxycytidine, restores expression of silenced RAR{beta}2 in breast cancer cells Mol. Cancer Ther., March 1, 2005; 4(3): 477 - 486. [Abstract] [Full Text] [PDF]

				C Jeronimo, R Henrique, J Oliveira, F Lobo, I Pais, M R Teixeira, and C Lopes Aberrant cellular retinol binding protein 1 (CRBP1) gene expression and promoter methylation in prostate cancer J. Clin. Pathol., August 1, 2004; 57(8): 872 - 876. [Abstract] [Full Text] [PDF]

				T. Kuroki, F. Trapasso, S. Yendamuri, A. Matsuyama, H. Alder, N. N. Williams, L. R. Kaiser, and C. M. Croce Allelic Loss on Chromosome 3p21.3 and Promoter Hypermethylation of Semaphorin 3B in Non-Small Cell Lung Cancer Cancer Res., June 15, 2003; 63(12): 3352 - 3355. [Abstract] [Full Text] [PDF]

				L. Cordain, S. Lindeberg, M. Hurtado, K. Hill, S. B. Eaton, and J. Brand-Miller Acne Vulgaris: A Disease of Western Civilization Arch Dermatol, December 1, 2002; 138(12): 1584 - 1590. [Abstract] [Full Text] [PDF]

				L. I. Chen, K. M. Sommer, and K. Swisshelm Downstream Codons in the Retinoic Acid Receptor beta -2 and beta -4 mRNAs Initiate Translation of a Protein Isoform That Disrupts Retinoid-activated Transcription J. Biol. Chem., September 13, 2002; 277(38): 35411 - 35421. [Abstract] [Full Text] [PDF]

				Q. Yang, M. Nakamura, Y. Nakamura, G. Yoshimura, T. Suzuma, T. Umemura, Y. Shimizu, I. Mori, T. Sakurai, and K. Kakudo Two-Hit Inactivation of FHIT by Loss of Heterozygosity and Hypermethylation in Breast Cancer Clin. Cancer Res., September 1, 2002; 8(9): 2890 - 2893. [Abstract] [Full Text] [PDF]

				J. Kwong, K.-W. Lo, K.-F. To, P. M. L. Teo, P. J. Johnson, and D. P. Huang Promoter Hypermethylation of Multiple Genes in Nasopharyngeal Carcinoma Clin. Cancer Res., January 1, 2002; 8(1): 131 - 137. [Abstract] [Full Text] [PDF]

				Q. Yang, G. Yoshimura, T. Suzuma, T. Tamaki, T. Umemura, M. Nakamura, Y. Nakamura, X. Wang, I. Mori, T. Sakurai, et al. Clinicopathological Significance of Fragile Histidine Triad Transcription Protein Expression in Breast Carcinoma Clin. Cancer Res., December 1, 2001; 7(12): 3869 - 3873. [Abstract] [Full Text] [PDF]