Title page for etd-0902110-170133


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URN etd-0902110-170133
Author Yen-Lin Huang
Author's Email Address No Public.
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Department Institute of Biomedical Sciences
Year 2009
Semester 2
Degree Master
Type of Document
Language English
Title The Role of Chibby as a Potential Tumor Suppressor Gene in Human Cervical Cancer
Date of Defense 2010-07-10
Page Count 46
Keyword
  • Wnt
  • oncogene
  • β-catenin
  • adenovirus
  • SiHa
  • HeLa
  • cervical cancer
  • chibby
  • Abstract The Wnt signaling pathway is highly conserved and participates in many important cellular functions including differentiation, embryonic development and tissue generations. β-catenin, the central mediator of the Wnt signaling, interacts with the TCF/LEF family of transcription factors in the nucleus and initiates downstream gene transcription. In addition, β-catenin is known as a proto-oncogene implicated in numerous cancers including colorectal, cervical, endometrial and skin cancer. Chibby (Cby) is evolutionarily conserved in many species and acts as a repressor of Wnt/β-catenin signaling. In our previous study, we have established that Cby over-expression attenuated β-catenin translocation to nucleus and its transcriptional activity. Thus, it was hypothesized that Cby may possess potential tumor suppressing capabilities. In the present study, we first explored endogenous Cby expression status in human cervical cancer cells: HeLa and SiHa cell lines. It was observed that Cby mRNA and protein levels were significantly down-regulated in both cancer lines compared with primary cervical cells. We then conducted functional assays of tumorigenicity on both cells using adenoviral-encoded Cby and its NLS (nuclear localization signaling) deleted variant (Cby∆NLS). It was found that gene delivery of Cby or Cby∆NLS inhibited the proliferation, invasiveness, and colony forming in HeLa and SiHa cells. Immunofluorescent analysis revealed that Cby or Cby∆NLS gene transfer reduced the expression of Ki-67, a cell proliferative marker. Furthermore, Cby or Cby∆NLS restoration induced apoptosis and perturbed cell cycle progression in both cervical cancer cells. Finally, Cby over-expression decreases the expression of β-catenin/TCF4 regulated genes such as c-myc and PCNA, which might contributed to the anti-neoplastic mechanism for Cby in cervical cancer cell lines. Our results strongly suggest that Cby may serve as a tumor suppressor gene during cervical carcinogenesis, and may facilitate in creation of new therapeutic methods.
    Advisory Committee
  • Long-Sheng Chang - chair
  • Yi-Ren Hong - co-chair
  • Ming-Hong Tai - advisor
  • Files
  • etd-0902110-170133.pdf
  • indicate in-campus access immediately and off_campus access in a year
    Date of Submission 2010-09-02

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