DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer

Oncogene. 1998 May 7;16(18):2381-7. doi: 10.1038/sj.onc.1201769.

Abstract

Using RNA fingerprinting (RAP) strategy and Northern blot analysis, we identified a differentially expressed sequence DOC-2 which is detectable in all normal human ovarian surface epithelial (HOSE) cell cultures but not in ovarian cancer cell lines and tissues. Subsequent cloning of DOC-2 from a cDNA library generated from the HOSE cells was carried out using the 3' and 5' RACE approach. A 3268 base pair full length cDNA of DOC-2 was isolated and sequenced. The predicted protein has a length of 770 amino acids. Homology search of all NCBI sequences indicated that the amino acid sequence of DOC-2 shares 93% homology with the mouse p96/mDab2 phosphoprotein and has a phosphotyrosine interacting domain (PID) and multiple SH3 binding motifs. Chromosomal localization by FISH showed that the DOC-2 gene is located on 5p13. Western blot analysis showed that the 105 kDa DOC-2 protein was down-regulated in all the carcinoma cell lines. In-situ immunohistochemistry performed on normal ovaries, and benign, borderline and invasive ovarian tumor tissues showed down regulation of DOC-2 protein particularly in serous ovarian tumor tissues. When DOC-2 was transfected into the ovarian carcinoma cell line SKOV3, the stable transfectants showed significantly reduced growth rate and ability to form tumors in nude mice. These data suggest that down-regulation of DOC-2 may play an important role in ovarian carcinogenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Chromosomes, Human, Pair 5
  • Female
  • Genes, Tumor Suppressor*
  • Humans
  • Molecular Sequence Data
  • Neoplasms, Glandular and Epithelial / genetics*
  • Ovarian Neoplasms / genetics*
  • Proteins / genetics*
  • RNA, Neoplasm / genetics
  • Sequence Homology, Amino Acid
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • DAB2 protein, human
  • Proteins
  • RNA, Neoplasm
  • Tumor Suppressor Proteins