title: Functional analysis of a cell cycle-associated, tumor-suppressive gene, protein tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma.
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.
authors.affiliation: Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People's Republic of China.
authors.forename: Arthur Kwok Leung
authors.initials: AK
authors.lastname: Cheung
authors.forename: Hong Lok
authors.initials: HL
authors.lastname: Lung
authors.forename: Siu Chun
authors.initials: SC
authors.lastname: Hung
authors.forename: Evan Wai Lok
authors.initials: EW
authors.lastname: Law
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.forename: Wing Lung
authors.initials: WL
authors.lastname: Yau
authors.forename: Dhinoth Kumar
authors.initials: DK
authors.lastname: Bangarusamy
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.forename: Edison Tak-Bun
authors.initials: ET
authors.lastname: Liu
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.forename: Chang-Wei
authors.initials: CW
authors.lastname: Kou
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Zabarovsky
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stanbridge
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics*; D002478:Cells, Cultured; D002893:Chromosomes, Human, Pair 3; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000502:physiology*
chemical_list: C516850:PTPRG protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5