The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

Ravi Kasiappan1, Hung-Ju Shih, Meng-Hsun Wu

  • 1Division of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.

Molecular Cancer
|December 9, 2010
PubMed
Abstract

Insights

The oncogenic MCT-1 protein counteracts the tumor suppressor p53 through multiple regulatory mechanisms, promoting tumor growth and overcoming p53

Area of Science:

  • Molecular oncology
  • Tumorigenesis research
  • Cancer biology

Background:

  • MCT-1 oncoprotein accelerates p53 degradation, enhancing xenograft tumorigenicity when p53 is lost.
  • The precise molecular interplay between MCT-1 and p53 in tumor development requires elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms by which MCT-1 influences p53 function and tumor development.
  • To explore the regulatory relationship between MCT-1 and p53 in cancer.

Main Methods:

  • Analysis of MCT-1 promoter activity and mRNA stability in response to wild-type and mutant p53.
  • Assessment of apoptotic events and tumor growth in p53-null and p53-positive lung cancer xenografts.
  • Evaluation of p53 inhibitors (MDM2, Pirh2, Cop1) expression stimulated by MCT-1.

Main Results:

  • MCT-1 is identified as a novel p53 target gene; functional p53 suppresses MCT-1, while MCT-1 negatively feedbacks on p53.
  • Oncogenic MCT-1 prevents apoptosis via p53-dependent and independent pathways, promoting tumorigenicity in vivo.
  • MCT-1 stimulates p53 inhibitors, rendering tumor growth resistant to p53 reactivation.

Conclusions:

  • The study establishes a complex opposition between MCT-1 and p53 across transcriptional control, mRNA metabolism, and protein expression.
  • MCT-1 oncogenicity effectively overcomes p53 tumor suppressive functions, driving persistent tumor progression.

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