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Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth.
- Source :
-
Oncogene [Oncogene] 2007 Jul 05; Vol. 26 (31), pp. 4580-9. Date of Electronic Publication: 2007 Feb 05. - Publication Year :
- 2007
-
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.
- Subjects :
- Amino Acid Sequence
Breast metabolism
Breast Neoplasms metabolism
Cell Proliferation
Down-Regulation
Female
Genes, Tumor Suppressor
Humans
Male
Molecular Sequence Data
Prostate metabolism
Prostatic Neoplasms metabolism
Reverse Transcriptase Polymerase Chain Reaction
GTPase-Activating Proteins metabolism
Neoplasms metabolism
Tumor Suppressor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 26
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 17297465
- Full Text :
- https://doi.org/10.1038/sj.onc.1210244