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

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

doi:10.1158/0008-5472.can-08-0904

Cited by 54 publications

(76 citation statements)

References 38 publications

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“…Matched normal NP and NPC biopsies from 30 NPC patients were collected from Queen Mary Hospital in Hong Kong from 2006 to 2009, as previously described (Cheung et al, 2008). All the biopsies were immediately stored in RNAlater solution (Ambion, Austin, TX, USA).…”

Section: Npc Tissue Specimensmentioning

confidence: 99%

“…The expression of long and short isoforms of FBLN2 in NPC cell lines and tumor biopsies was analyzed by RT-PCR. Q-PCR was performed as previously described (Cheung et al, 2008) in a Step-One Plus machine using SYBR-green PCR core reagent kits (Applied Biosystems, Foster City, CA, USA). We analyzed expression of FBLN2, MMP2, MMP9 and VEGF using gene-specific primers (Supplementary Table S2).…”

Section: Rt-pcr and Real-time Q-pcr Analysismentioning

confidence: 99%

“…Western blot analysis of FBLN2 was performed as previously described (Cheung et al, 2008). Polyclonal antiserum against the full-length FBLN2 protein was prepared as described (Pan et al, 1993).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Bisulfite modification of DNA was performed as previously described (Cheung et al, 2008). The 591-bp putative FBLN2 CpG island in the promoter region mapping to position chr3:13565415-13566008 has been described (Supplementary Figure S1; Dunwell et al, 2009).…”

Section: Methylation Analysismentioning

confidence: 99%

“…Chromosome 3p shows a high frequency of allelic loss in nasopharyngeal carcinoma (NPC) tumors and has an important role in NPC suppression (Mutirangura et al, 1997;Senchenko et al, 2004;Yau et al, 2006;Cheung et al, 2008). NotI chromosome 3-specific microarray profiling is useful for screening for genes inactivated by deletion and/or hypermethylation.…”

Section: Introductionmentioning

confidence: 99%

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Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma

et al. 2011

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Section: Npc Tissue Specimensmentioning

confidence: 99%

Section: Rt-pcr and Real-time Q-pcr Analysismentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Methylation Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma

et al. 2011

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Functional characterization of THY1 as a tumor suppressor gene with antiinvasive activity in nasopharyngeal carcinoma

Lung

Cheung

Cheng

et al. 2010

Intl Journal of Cancer

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THY1 was previously identified as a candidate tumor suppressor gene (TSG) associated with lymph node metastases in nasopharyngeal carcinoma (NPC) through functional studies. It was identified by oligonucleotide microarray analysis as an interesting differentially expressed gene. However, direct functional evidence is still lacking for THY1 being a TSG in NPC, as in vivo tumorigenicity assays have not been previously reported in our last study of THY1. In this study, a tetracycline-inducible expression vector, pETE-Bsd, was used to obtain stable transfectants of THY1. The stringent in vivo tumorigenicity assay results show that the activation of THY1 suppresses tumor formation of HONE1 cells in nude mice, and the tumor formation ability was restored in the presence of doxycycline (a tetracycline analog), when the gene is shut off. Functional inactivation of this gene is observed in all the tumors derived from the tumorigenic transfectant. The tumor suppressive effect could be repressed by knockdown of THY1 expression in nontumorigenic microcell hybrids. Further studies indicate that expression of THY1 inhibits HONE1 cell growth in vitro by arresting cells in G 0 /G 1 phase. It greatly reduces the ability for anchorage-independent growth. The invasiveness of HONE1 cells was also inhibited by the expression of THY1. These findings suggest that THY1 is a TSG in NPC, which is involved in invasion and shows an association with tumor metastasis. Taken together, THY1 clearly plays an important functional role in tumor suppression in NPC.THY1 (CD90) is a cell surface glycoprotein of 25-37 kDa localized on the outer leaflet of cell membranes, enriched in lipid raft microdomains. Human THY1 maps to chromosome 11q22.3. It is expressed on various cell types, including human fibroblasts, neurons, blood stem cells and endothelial cells as well as murine T cells.1 THY1 is involved in T cell activation and the other nonimmunologic functions including inhibition of neurite outgrowth, apoptotic signaling, leukocyte and melanoma cell adhesion and migration and fibroblast proliferation and migration. 2,3 Taken together, these functions suggest that THY1 is an important mediator of cell-cell and cell-matrix interactions. In T cells, it is reported to function in cell adhesion with the bone marrow stroma.1 Surface expression of THY1 promotes focal adhesion in fibroblasts. 2In cancers, THY1 was initially found to be differentially expressed in tumorigenic and nontumorigenic hybrid clones derived from the transfer of chromosome 11 into the human ovarian cancer cell line SKOV-3. 4 The later functional studies also suggest that THY1 is associated with tumor suppression in human ovarian cancer.5 A recent study shows that loss of THY1 expression is correlated with poor survival rate in neuroblastoma patients.6 THY1 is also involved in the adhesion of melanoma cells to the human dermal microvascular endothelial cells.7 THY1 is a cell surface marker, which has been used to identify local and circulating liver cancer stem cells. 8,9 Nasopharyn...

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Metastatic cutaneous squamous cell carcinoma shows frequent deletion in the protein tyrosine phosphatase receptor Type D gene

Lambert

Harwood

Purdie

et al. 2011

Intl Journal of Cancer

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Cutaneous squamous cell carcinoma (cSCC) is the second most common form of nonmelanoma skin cancer (NMSC), and its incidence is increasing rapidly. Metastatic cSCC accounts for the majority of deaths associated with NMSC, but the genetic basis for cSCC progression remains poorly understood. A previous study identified small deletions (typically <1 Mb) in the protein tyrosine phosphatase receptor Type D (PTPRD) gene that segregated with more aggressive cSCC. To investigate the apparent association between deletion within PTPRD and cSCC metastasis, a series of 74 formalin-fixed paraffin-embedded tumors from 31 patients was analyzed using a custom Illumina 384 SNP microarray. Deletions were found in 37% of patients with metastatic cSCC and were strongly associated with metastatic tumors when compared to those that had not metastasized (p 5 0.007). Subsequent mutation analysis revealed a higher mutation rate for PTPRD than has been reported in any other cancer type, with 37% of tumors harboring a somatic mutation. Conversely, bisulfite sequencing showed that methylation was not a mechanism of PTPRD disruption in cSCC. This is the first report to observe an association between deletion within PTPRD and metastatic disease and highlights the potential use of these deletions as a diagnostic biomarker for tumor progression. Combined with the high mutation rate observed in our study, PTPRD is one of the most commonly altered genes in cSCC and warrants further investigation to determine its significance for metastasis in other tumor types.Nonmelanoma skin cancer (NMSC) has a predicted prevalence equal to that of all other cancers combined and its incidence is increasing.1 There are more than 81,500 new cases of NMSC diagnosed annually in the United Kingdom alone, placing a heavy burden on both patients and healthcare resources.2 Despite accounting for only 20% of total NMSC cases, cutaneous squamous cell carcinoma (cSCC) is responsible for the majority of NMSC deaths, largely as a result of metastatic disease. A subset of immunosuppressed individuals, such as organ transplant recipients on long-term immunosuppressive drugs, develop particularly aggressive tumors with an increased risk of metastasis.3 Risk factors for metastasis include poor differentiation of the tumor cells, large tumor size, tumor depth >5 mm, immunosuppression and localization on the ear and lip. [4][5][6][7] Metastatic cSCC is currently treated by surgical intervention and/or chemotherapy or radiotherapy and is associated with a poor outcome. 8Despite the well-established role of ultraviolet radiation (UVR) in the etiology of cSCC, the molecular events underlying its development remain largely undefined. Inactivation of the tumor suppressor genes TP53 and p16INK4A is a common and early event in cSCC pathogenesis and is characteristic of all histological grades of tumor. 9,10 Recently, genotyping of 60 cSCC identified high rates of loss of heterozygosity (LOH)

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

Cited by 54 publications

References 38 publications

Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma

Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma

Functional characterization of THY1 as a tumor suppressor gene with antiinvasive activity in nasopharyngeal carcinoma

Metastatic cutaneous squamous cell carcinoma shows frequent deletion in the protein tyrosine phosphatase receptor Type D gene

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