The Expression Of DMBT1 Gene In Prostate Cancer And Its Clinical Significance

Part One Screen the treated and untreated prostate cancer cell lines by Genome MicroarrayObjectives:To identify some genes that may be regulated by methylation during the prostate tumorigenesis.Methods:After treating prostate cell lines LNCaP and PC-3 with DNA methyltransferase inhibitor--5-aza-2'-deoxycytidine(5-aza-dc),we used the Whole Human Genome Oligo Microarray to screen the treated cells and the controlled groups to identify some genes which restored expression after anti-methylation.Results:The expression of DMBT1 gene(Deleted in Malignant Brain Tumor)was observed to be significantly up-regulated in treated PC-3 cell lines than controlled cell lines, however no similar expression change was observed in both treated and controlled LNCaP cell lines.Conclusions:Anti-methylation with DNA methyltransferase inhibitor(5-aza-dc)is able to up-regulate the expression of DMBT1 in PC-3 cell lines.This implies that the expression of DMBT1 gene may be related to DNA methylation.Further tissue evaluation was necessary to confirm the expression of DMBT1 gene in prostate cancer.Partâ…¡The expression of DMBT1 in prostate cancer cell lines and tissues and its clinical significanceObjectives:To observe the expression of DMBT1 gene in both prostate cancer cell lines and tissues,then to evaluate the potential correlation between DMBT1 expressions and clinical and pathologic features such as age,PSA,clinical stage,tumor grade and bone metastasis.Methods:The expressions of DMBT1 in both mRNA and protein levels were detected by real-time quantitative PCR and western blot in prostate cancer cell lines(LNCaP & PC-3) and prostatic tissues from 16 benign lesions and 39 carcinomas.The correlation between gene expression level and clinical/pathologic features was analyzed using Spearman Correlation method by the software SPSS 13.0.Results:The mRNA expression of DMBT1 in both PC-3 and LNCaP cell lines were down-regulated compared to normal tissues and the fold changes in LNCaP cell lines was significantly obvious.Similar to the results of genome microarray,anti-methylation with 5-aza-dc may significantly restore the expression level of DMBT1 in PC-3 cell lines than LNCaP cell lines.Compared to the normal prostatic tissues,both mRNA and protein expressions of DMBT1 gene were significantly down-regulated in whole prostate cancer tissue samples.The statistical results showed that the expression levels of DMBT1 were correlated to clinical stage and osseous metastasis,but not correlated to patient age,PSA level and tumor grade at diagnosis.Conclusions:Real-time quantitative PCR is recommended to detect the mRNA expression compared to traditional RT-PCR.DMBT1 is down-regulated in prostate cancer tissues and cell lines,but the mechanism is unknown.The DMBT1 gene is confirmed to be a potential biomarker in identification of hormonal independent subgroup from hormonal dependent prostatic carcinomas,as well as the prognostic value with its correlation to clinical stage and tumor grade.It is necessary to elucidate the regulation mechanism of DMBT1 and its contribution in cell physiology and tumorigenesis.