Functional Analysis of a Cell Cycle–Associated, Tumor-Suppressive Gene, Protein Tyrosine Phosphatase Receptor Type G, in Nasopharyngeal Carcinoma

Arthur Kwok Leung Cheung, Hong Lok Lung, Siu Chun Hung, Evan Wai Lok Law, Yue Cheng, Wing Lung Yau, Dhinoth Kumar Bangarusamy, Lance D. Miller, Edison Tak Bun Liu, Jian Yong Shao, Chang Wei Kou, Daniel Chua, Eugene R. Zabarovsky, Sai Wah Tsao, Eric J. Stanbridge, Maria Li Lung*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

53 Citations (Scopus)

Abstract

Functional studies to identify the potential role of a chromosome 3p14-21 gene, protein tyrosine phosphatase receptor type G (PTPRG), were performed. PTPRG was identified as a candidate tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC) by differential gene profiling of tumorigenic and nontumorigenic NPC chromosome 3 microcell hybrids (MCH). Down-regulation of this gene was found in tumor segregants when compared with their corresponding tumor-suppressive MCHs, as well as in NPC cell lines and tumor biopsies. Promoter hypermethylation and loss of heterozygosity were found to be important mechanisms contributing to PTPRG silencing. PTPRG overexpression in NPC cell lines induces growth suppression and reduced anchorage-independent growth in vitro. This is the first study to use a tetracycline-responsive vector expression system to study PTPRG stable transfectants. Results indicate its ability to induce significant tumor growth suppression in nude mice under conditions activating transgene expression. These studies now provide functional evidence indicating critical interactions of PTPRG in the extracellular matrix milieu induce cell arrest and changes in cell cycle status. This is associated with inhibition of pRB phosphorylation through down-regulation of cyclin D1. These novel findings enhance our current understanding of how PTPRG may contribute to tumorigenesis.

Original languageEnglish
Pages (from-to)8137-8145
Number of pages9
JournalCancer Research
Volume68
Issue number19
DOIs
Publication statusPublished - 1 Oct 2008
Externally publishedYes

Scopus Subject Areas

  • Oncology
  • Cancer Research

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