Allelic losses of chromosomes 3 and 14 are common events in nasopharyngeal carcinoma (NPC) patients. This suggests these two chromosomes play important roles in NPC development. In this current study, using the microcell-mediated chromosome transfer (MMCT) approach, candidate tumor suppressor genes (TSGs) located on these two important chromosomes were identified. Two candidate genes, Protein tyrosine phosphatase receptor type G (PTPRG) and Mirror-image polydactyly 1 (MIPOL1), located on chromosomes 3 and 14, respectively, were studied in depth in order to understand more about their functional roles during NPC development. An oligonucleotide microarray analysis was performed to investigate the global gene expression changes of chromosome 14 tumor suppressive microcell hybrids (MCHs) an...[ Read more ]

Allelic losses of chromosomes 3 and 14 are common events in nasopharyngeal carcinoma (NPC) patients. This suggests these two chromosomes play important roles in NPC development. In this current study, using the microcell-mediated chromosome transfer (MMCT) approach, candidate tumor suppressor genes (TSGs) located on these two important chromosomes were identified. Two candidate genes, Protein tyrosine phosphatase receptor type G (PTPRG) and Mirror-image polydactyly 1 (MIPOL1), located on chromosomes 3 and 14, respectively, were studied in depth in order to understand more about their functional roles during NPC development. An oligonucleotide microarray analysis was performed to investigate the global gene expression changes of chromosome 14 tumor suppressive microcell hybrids (MCHs) and their corresponding tumorigenic tumor segregants (TSs).

Down-regulation of PTPRG was found in NPC cell lines and patient biopsies. It is up-regulated in chromosome 3 MCHs and down-regulated in TSs. Over-expression of PTPRG inhibits colony formation, anchorage-independent growth, and 3D culture spheroid formation ability. In vivo tumorigenicity assay, using the tet-off inducible system, shows PTPRG expression induces tumor suppression, when expressed. Interaction of PTPRG and the extracellular matrix was proven to induce cell cycle arrest through the cyclin D/pRB pathway.

Chromosome 14 MMCT was performed; five tumor suppressive MCHs containing intact exogenous chromosome 14 were established. Four tumor suppressive critical regions (CRs) were identified. A candidate TSG, MIPOL1, was chosen for further study. MIPOL1 was down-regulated in NPC cell lines and patient biopsies. Its up-regulation in chromosome 14 MCHs and down-regulation in TSs can be observed. MIPOL1 can suppress tumor formation in in vivo tumorigenicity assays and is able to induce p21(WAF1/CIP1) and p27(KIP1) protein expression.