Abstract
BackgroundThe transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage.MethodsGenomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test.ResultsWe first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage.ConclusionOur results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients are not significantly different. Although expression of trpv6 transcripts correlates with aggressive potential of prostate cancer, the TRPV6 genotype does not correlate with the onset of prostate cancer, with the Gleason score and the tumour stage.
Highlights
The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca2+ selective cation channel
Because TRPV6 transcripts are present in advanced prostatic adenocarcinoma samples we asked if the TRPV6 genotype may influence the progression of prostate cancer
TRPV6 transcripts are expressed in patients with advanced prostatic adenocarcinoma but are not detectable in healthy and benign prostate tissue
Summary
The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca2+ selective cation channel. Intracellular calcium levels are highly regulated to achieve precise regulation of cell signalling pathways. Among the TRP-calcium channel family TRPM4 has been shown to be expressed in benign and malign prostate tissue [9]whereas TRPM8 is overexpressed in prostate cancer [6]. In contrast TRPV6 is a highly Ca-selective cation channel and its transcripts are overexpressed in prostatic adenocarcinoma but undetectable in healthy and benign prostate tissue [7,10]. In prostate tissue the expression of TRPV6 is strictly correlated with the Gleason grading and the tumour staging implying that TRPV6 is an indicator for the metastatic potential of prostatic adenocarcinoma and a potential target for drugs which may be used to treat this disease [11]. Overexpression of TRPV6 stimulates proliferation of HEK293 cells in a calcium dependent manner [12]
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