Downregulation of C1‐TEN expression in human cancer

Abstract

C1‐TEN is a novel intracellular protein homologous to both tensin and to PTEN. C1‐TEN overexpression in mammalian cells alters cell morphology, inhibits cell proliferation and migration and enhances apoptosis. These effects are coupled to a downregulation of Akt signalling, possibly through C1‐TEN phosphatase activity. The aim of this study was to investigate the expression of C1‐TEN and its sister protein Tensin3 in human cancer. mRNA expression of both C1‐TEN and Tensin3 were analysed from total RNA from a human renal cell carcinoma kidney tumour by RT‐PCR, together with adjacent normal tissue from the same donor. Also, a panel of 20 human cancer cell lines from various tumours were analysed. We also probed eight human cancer cells lines for C1‐TEN mRNA expression by northern blot. In addition, we analysed protein expression in extracts of the same cell lines by western blot using anti‐C1‐TEN antibodies. C1‐TEN mRNA expression was greatly reduced (80%) in human kidney tumour as compared to adjacent normal tissue. Furthermore, both C1‐TEN mRNA and protein expression were absent in all but two human cancer cell lines. The profile of Tensin3 expression was higher and more variable amongst the cell lines, although its expression was also reduced in kidney tumour extact. These results show that expression of C1‐TEN, which we have previously shown to be a negative signalling regulator for growth, survival and migration, is downregulated in cancer. Loss of C1‐TEN may be a consequence of, or a contributing factor to, tumourigenesis. Furthermore, Tensin3, also a putative phosphatase, appears also to correlate with tumorigenesis. We are currently investigating the putative phsophatase activity of both proteins, as well as their expression in more human cancers.