Human secreted frizzled-related protein is down-regulated and induces apoptosis in human cervical cancer

Je Sang Ko, Ki Sung Ryu, Young Han Lee, Doe Sun Na, Yoon Suk Kim, Young Mi Oh, In Sik Kim, Jin Woo Kim

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

To identify genes involved in cervical carcinogenesis, the mRNA differential display method was used. A 220-bp cDNA fragment called CA11 was present in normal cervical tissue but not in primary cervical cancer tissue or cervical cancer cell lines. CA11 exhibited 98% homology with the recorded human secreted frizzled-related protein (hsFRP) sequence. A dominant hsFRP mRNA transcript of approximately 4.6 kb was present in three normal cervical tissues examined. Expression of the transcript was nearly absent from three cervical cancer tissues and from five human cervical cancer-derived cell lines. Results from in situ hybridization showed that the hsFRP transcript was confined to the normal cervical epithelial layer. When hsFRP-trans-fected HeLa and CUMC-6 cervical cancer cells were cultured in serum-free medium, most of the cells died within 8 days. This effect is associated with the apoptotic process. The caspase-3 inhibitor 1, Ac-DEVD-CHO, blocked hsFRP-induced apoptotic cell death. Additionally, cleavage of poly (ADP-ribose) polymerase in hsFRP-transfected cells was confirmed by colorimetric assay. These results indicate that the hsFRP gene probably functions as a tumor suppressor in normal cervical epithelium and down-regulation of hsFRP contributes to development of cervical cancer.

Original languageEnglish
Pages (from-to)280-287
Number of pages8
JournalExperimental Cell Research
Volume280
Issue number2
DOIs
Publication statusPublished - 2002 Nov 25
Externally publishedYes

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Keywords

  • β-catenin
  • Apoptosis
  • Cervical cancer
  • Human secreted frizzled-related protein
  • Tumor suppressor

ASJC Scopus subject areas

  • Cell Biology

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