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

S. C. Mok, W. Y. Chan, K. K. Wong, K. K. Cheung, C. C. Lau, S. W. Ng, A. Baldini, C. V. Colitti, C. O. Rock, R. S. Berkowitz

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2381-2387
Number of pages7
JournalOncogene
Volume16
Issue number18
Publication statusPublished - May 7 1998

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Keywords

  • Cancer
  • Dab
  • DOC-2
  • Ovary
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Mok, S. C., Chan, W. Y., Wong, K. K., Cheung, K. K., Lau, C. C., Ng, S. W., Baldini, A., Colitti, C. V., Rock, C. O., & Berkowitz, R. S. (1998). DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer. Oncogene, 16(18), 2381-2387.