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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Com-1/ p8 acts as a putative tumour suppressor in prostate cancer.

Com-1, candidate of metastasis-1, also known as p8, is a recently discovered molecule with a putative role in determining the metastatic nature of cancer cells. We have investigated the expression of Com-1 in normal and malignant human prostate tissues and its molecular interaction within prostate cancer cells. The expression of Com-1 in human prostate tissues and prostate cancer cell lines was assessed at both the mRNA and protein levels, by RT-PCR and immunohistochemistry. The staining intensity of Com-1 was semiquantified using computer assisted image analysis. Full- length Com-1 cDNA was isolated from normal mammary tissues. Ribozyme transgenes that specifically target human Com-1 were constructed using the pEF6/V5-His vector. The growth of prostate cancer cells in vitro and tumour growth in vivo (athymic mice model) following Com-1 overexpression in prostate cancer cells were determined. In normal prostate tissues, the epithelial cells strongly stained Com-1, both in the cytoplasm and in the nucleus. In contrast, prostate cancer cells in tumour tissue showed substantially reduced Com-1 staining levels (p<0.05 compared to normal cells for both cytoplasmic and nucleus staining), whereas the prostate cancer cell lines PC-3, DU145 and CA-HPV10 widely expressed Com-1. Transfection of these cells with hammerhead ribozyme transgenes resulted in the loss of expression of the Com-1 transcript. Using an in vitro invasion assay we found that the loss of Com-1 from prostate cancer cells increased their invasiveness. Knockout of Com-1 also resulted in the accelerated growth of all three cell lines. Forced overexpression of Com-1/ p8 in prostate cancer cells was able to reverse the changes in invasiveness and growth seen with the Com-1 knock-out cells. In a spontaneous tumour model, it was demonstrated that PC-3 cells with forced overexpression of Com-1 (PC-3com1Exp) had a significantly slower rate of growth compared with control cells (tumour size 36.6+/-31.2 vs 114.3+/-68.1 mm(3), for tumours from PC-3com1Exp and control PC-3 cells, respectively, p=0.0023). In conclusion, Com-1/ p8 was expressed at lower levels in human prostate cancer cells compared with normal epithelial cells. Com-1/ p8 levels are inversely correlated with the invasiveness and growth of prostate cancer cells in vitro and the overexpression of Com-1 reduced the growth of prostate tumours in vivo. Com-1/ p8 is a potential tumour suppressor in human prostate cancer.[1]

References

  1. Com-1/p8 acts as a putative tumour suppressor in prostate cancer. Jiang, W.G., Davies, G., Martin, T.A., Kynaston, H., Mason, M.D., Fodstad, O. Int. J. Mol. Med. (2006) [Pubmed]
 
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