Functional analysis of a cell cycle-associated, tumor-suppressive gene, protein tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma.
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.
Cheung
Arthur Kwok Leung
AK
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.
Lung
Hong Lok
HL
Hung
Siu Chun
SC
Law
Evan Wai Lok
EW
Cheng
Yue
Y
Yau
Wing Lung
WL
Bangarusamy
Dhinoth Kumar
DK
Miller
Lance D
LD
Liu
Edison Tak-Bun
ET
Shao
Jian-Yong
JY
Kou
Chang-Wei
CW
Chua
Daniel
D
Zabarovsky
Eugene R
ER
Tsao
Sai Wah
SW
Stanbridge
Eric J
EJ
Lung
Maria Li
ML
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*
C516850:PTPRG protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5