Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth

Oncogene. 2007 Jul 5;26(31):4580-9. doi: 10.1038/sj.onc.1210244. Epub 2007 Feb 5.

Abstract

Two related Rho GTPase-activating proteins, DLC-1 (deleted in liver cancer 1) and DLC-2, are emerging as bona fide tumor suppressor genes that inhibit cancer cell growth. In this report, we characterized a gene on chromosome Xq13 that encodes DLC-3 (also known as KIAA0189 and STARD8), a third member of the DLC family. The DLC-3 gene has transcripts with alternative 5' ends, one of which, DLC-3alpha, encodes an 1103-amino acid polypeptide highly similar to DLC-1 and DLC-2. A second isoform (DLC-3beta) would yield a protein lacking the N-terminal sterile alpha motif domain. The DLC-3 gene is widely expressed in normal tissues, but DLC-3 mRNA levels were low or absent in a significant number of breast, ovarian, liver and prostate cancer cell lines. Using a cancer profiling array to compare matched tumor and normal human tissues, downregulation of DLC-3 mRNA was observed in kidney, lung, ovarian, uterine and breast cancer samples. By quantitative reverse transcriptase-polymerase chain reaction, DLC-3 expression was reduced in primary prostate carcinomas relative to normal prostate tissue. Transfection of human breast and prostate cancer cells with a DLC-3alpha expression vector inhibited cell proliferation, colony formation and growth in soft agar. These results indicate that deregulation of DLC-3 may contribute to breast and prostate tumorigenesis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Breast / metabolism
  • Breast Neoplasms / metabolism
  • Cell Proliferation
  • Down-Regulation
  • Female
  • GTPase-Activating Proteins / metabolism*
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • Molecular Sequence Data
  • Neoplasms / metabolism*
  • Prostate / metabolism
  • Prostatic Neoplasms / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins / genetics*

Substances

  • DLC1 protein, human
  • GTPase-Activating Proteins
  • Tumor Suppressor Proteins
  • rho GTPase-activating protein