This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Kim, H. Articles by Pollack, J. R. Search for Related Content PubMed PubMed Citation Articles by Kim, H. Articles by Pollack, J. R.

The Retinoic Acid Synthesis Gene ALDH1a2 Is a Candidate Tumor Suppressor in Prostate Cancer

Departments of ¹ Pathology and ² Urology, Stanford University, Stanford, California; ³ Department of Biochemistry, Vanderbilt University Medical Center, Nashville, Tennessee; and ⁴ Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

Requests for reprints: Jonathan R. Pollack, Department of Pathology, Stanford University School of Medicine, 269 Campus Drive, CCSR 3245A, Stanford, CA 94305-5176. Phone: 650-736-1987; Fax: 650-736-0073; E-mail: pollack1{at}stanford.edu.

Prostate cancer is the most common cancer among men in the United States, and aberrant DNA methylation is known to be an early molecular event in its development. Here, we have used expression profiling to identify novel hypermethylated genes whose expression is induced by treatment of prostate cancer cell lines with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-aza-dC). Of the 271 genes that were induced by 5-aza-dC treatment, 25 also displayed reduced expression in primary prostate tumors compared with normal prostate tissue, and the decreased expression of only one gene, aldehyde dehydrogenase 1 family, member A2 (ALDH1a2), was also associated with shorter recurrence-free survival. ALDH1a2 encodes an enzyme responsible for synthesis of retinoic acid (RA), a compound with prodifferentiation properties. By immunohistochemistry, we observed that ALDH1a2 was expressed in epithelia from normal prostate but not prostate cancer. Using bisulfite sequencing, we determined that the ALDH1a2 promoter region was significantly hypermethylated in primary prostate tumors compared with normal prostate specimens (P = 0.01). Finally, transfection-mediated reexpression of wild-type ALDH1a2 (but not a presumptive catalytically dead mutant) in the prostate cancer cell line DU145 resulted in decreased colony growth (P < 0.0001), comparable with treatment with either 5-aza-dC or RA. Taken together, our findings implicate ALDH1a2 as a candidate tumor suppressor gene in prostate cancer and further support a role of retinoids in the prevention or treatment of prostate cancer.

This article has been cited by other articles:

				J. Lapointe, C. Li, C. P. Giacomini, K. Salari, S. Huang, P. Wang, M. Ferrari, T. Hernandez-Boussard, J. D. Brooks, and J. R. Pollack Genomic Profiling Reveals Alternative Genetic Pathways of Prostate Tumorigenesis Cancer Res., September 15, 2007; 67(18): 8504 - 8510. [Abstract] [Full Text] [PDF]

				M. Zaitseva, B. J. Vollenhoven, and P. A.W. Rogers Retinoic acid pathway genes show significantly altered expression in uterine fibroids when compared with normal myometrium Mol. Hum. Reprod., August 1, 2007; 13(8): 577 - 585. [Abstract] [Full Text] [PDF]

				S. E. Trasino, E. H. Harrison, and T. T. Y. Wang Androgen Regulation of Aldehyde Dehydrogenase 1A3 (ALDH1A3) in the Androgen-Responsive Human Prostate Cancer Cell Line LNCaP Experimental Biology and Medicine, June 1, 2007; 232(6): 762 - 771. [Abstract] [Full Text] [PDF]