Loss of DMBT1 expression in human prostate cancer and its correlation with clinical progressive features.

OBJECTIVES

To investigate alterations of DMBT1 in prostate cancer and determine the correlation of its alterations to the clinicopathologic features of prostate cancer. DMBT1 has been proposed as a candidate tumor suppressor gene for epithelial cancer.

METHODS

The alterations of DMBT1 expression after treatment with DNA methyltransferase inhibitor in 2 prostate cancer cell lines (LNCaP and PC-3) were analyzed by genome microarray and real-time polymerase chain reaction (PCR). A total of 36 prostate cancer tissues and 16 benign prostatic tissues were evaluated with reverse transcription-PCR, Western blot, and immunohistochemistry for DMBT1 expression.

RESULTS

Treatment with 5-aza-2'-deoxycytidine reactivated expression of DMBT1 in PC3 cells, but not in LNCaP cells. Downregulation or loss of DMBT1 mRNA and protein expression was observed in prostate cancer, but not in benign tissues. Immunostaining analysis showed DMBT1 protein was absent in 14 cancer samples with Gleason score of 8-10 and weakly stained in 16 cancer samples with Gleason score of 4-7, compared with strong immunostaining in all 15 benign prostatic tissues. Loss of DMBT1 expression was correlated with local invasion (P = .048) and bone metastasis (P = .039) but was not correlated with patient age, prostate-specific antigen level, or tumor grade at diagnosis.

CONCLUSIONS

Our study provides evidence that loss of DMBT1 expression is associated with prostate cancer, suggesting that DMBT1 may function as a tumor suppressor gene in prostate carcinogenesis.