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

Int J Mol Med. 2006 Nov;18(5):981-6.


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 mm3, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / analysis
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cell Line, Tumor
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • RNA, Catalytic / genetics
  • RNA, Catalytic / metabolism
  • RNA, Messenger / analysis
  • Transcriptional Activation
  • Transfection
  • Transgenes
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*


  • Basic Helix-Loop-Helix Transcription Factors
  • NUPR1 protein, human
  • Neoplasm Proteins
  • RNA, Catalytic
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • hammerhead ribozyme