Study of L-DOPA decarboxylase (DDC) in prostate tissues and cancer cell lines.

L-Dopa decarboxylase (DDC) is a pyridoxal 5’-phosphate-dependent enzyme that catalyses the decarboxy-lation of L-3,4-dihydroxyphennylalanine (L-Dopa) to dopam-ine (DA) and 5-hydroxytryptophan (5-HTP) to serotonine. Interestingly, it was found to be overexpressed at mRNA and protein level in small-cell carcinoma of the lung, neuroblas-toma, protopathic cancer of ileus and gastric cancer peritoneal dissemination. Previously, DDC was identified as a novel androgen receptor (AR) co-activator protein that co-expressed with AR in a subset of neuroendocrine (NE) prostate cancer cells.

Purpose:

The aim of this study was to investigate if DDC is expressed in prostate cancer cells and to evaluate its clinical potential in prostate cancer (CaP).

Materials & Methods:

Total RNA was isolated from 120 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients, as well as from LNCaP and PC3 prostate cancer cell lines. A highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDCmRNA quantification has been developed using the SYBR Green® chemistry. cDNA was prepared by reverse transcription using oligo-dT primers. Quantitative real time PCR was performed for DDC using gene-specific primers. Relative quantification analysis was made using the comparative C_T (2^-ÄÄCT) method and the LNCaP prostate cancer cell line as a calibrator. GAPDH was used as a housekeeping gene.

Results:

DDCwas found to be highly expressed in LNCaP prostate cancer cell line but not in PC3 cells. DDC was found to be over expressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (p<0.001). Logistic regression and ROC curve analysis have demonstrated that the DDC expression have significant discriminatory value, suggesting that it could be an additional marker for CaP and BPH diaforodiagnosis in prostate cancer. DDC expression was also found to be related with tumor progression. Conclusions: Our data reveal the potential of DDC expression, at the mRNA level, as a biomarker in diagnosis and prognosis of prostate cancer.

Acknowledgements: The project is co-funded by the European Social Fund and National Resources – (EPEAEK II) PYTHAGORAS II.