Assignment&lt;footref rid="foot01"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/footref&gt; and cloning of mouse &lt;i&gt;Arhgap7&lt;/i&gt; to chromosome 8A4–B2, a conserved syntenic region of human chromosome 8p22→p21

Yuan, Bao‐Zhu; Yang, Y.; Keck-Waggoner, Catherine L.; Zimonjic, D.B.; Thorgeirsson, Snorri S.; Popescu, N.C.

doi:10.1159/000015462

Cited by 8 publications

(7 citation statements)

References 3 publications

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“…DLC1 is a gene located in 8p22‐21.3 that belong to the GTPase‐activiating proteins Rho family, which binds to human tensins to suppress tumor growth by regulating actin adhesion 45, 46. Seng et al .…”

Section: Discussionmentioning

confidence: 99%

“…44 DLC1 is a gene located in 8p22-21.3 that belong to the GTPase-activiating proteins Rho family, which binds to human tensins to suppress tumor growth by regulating actin adhesion. 45,46 Seng et al showed DLC1 was a downregulated by methylation in NPC and suppression of growth in the CNE cell line. 18 We confirmed the ability of DLC1 to decrease colony formation and decrease invasion capacity in another NPC cell line and showed decreased invasion properties.…”

Section: Discussionmentioning

confidence: 99%

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A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma

Loyo¹,

Brait²,

Kim³

et al. 2011

Intl Journal of Cancer

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Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique genetic, viral and environmental characteristic that distinguishes it from other head and neck carcinomas. The clinical management of NPC remains challenging largely due to the lack of early detection strategies for this tumor. In our study, we have sought to identify novel genes involved in the pathogenesis of NPC that might provide insight into this tumor's biology and could potentially be used as biomarkers. To identify these genes, we studied the epigenetics of NPC by characterizing a panel of methylation markers. Eighteen genes were evaluated by quantitative methylation-specific polymerase chain reaction (PCR) in cell lines as well as in tissue samples including 50 NPC tumors and 28 benign nasopharyngeal biopsies. Significance was evaluated using Fisher's exact test and quantitative values were optimized using cut off values derived from receiver-operator characteristic curves. The methylation status of AIM1, APC, CALCA, deleted in colorectal carcinomas (DCC), DLEC, deleted in liver cancer 1 (DLC1), estrogen receptor alpha (ESR), FHIT, KIF1A and PGP9.5 was significantly associated with NPC compared to controls. The sensitivity of the individual genes ranged from 26 to 66% and the specificity was above 92% for all genes except FHIT. The combination of PGP9.5, KIF1A and DLEC had a sensitivity of 84% and a specificity of 92%. Ectopic expression of DCC and DLC1 lead to decrease in colony formation and invasion properties. Our results indicate that methylation of novel biomarkers in NPC could be used to enhance early detection approaches. Additionally, our functional studies reveal previously unknown tumor suppressor roles in NPC.Nasopharyngeal carcinoma (NPC) is a relatively rare head and neck malignancy in the United States. The global age adjusted incidence is one per 100,000 per year representing 0.7% of all cancers.1 In contrast, certain southern regions of China have an incidence as high as 50 cases per 100,000 per year.2 In fact in Hong Kong, NPC is the leading cancer in men age 20-44 years representing 25% of all cancers.3 NPC is particularly interesting because of its unique genetic, viral and environmental factors. Epstein-Barr virus (EBV) is a critical factor for malignant transformation in NPC. 4 However, only a small fraction of widespread EBV-infected patients will develop a NPC and not all NPC are EBV positive.5 EBV is present in more than 95% of the endemic Type I non-keratinizing lesions, while 30-50% of the Type II keratinizing lesions in the non endemic regions are EBV negative.6 Aside from EBV, environmental exposure to food preservatives in food, salted fish and occupational exposures have been related to increased NPC incidence. 3The initial presentation of NPC varies widely but rarely is the disease localized to the nasopharynx. Commonly, patients present with advanced disease that has metastasized to the

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma

Loyo¹,

Brait²,

Kim³

et al. 2011

Intl Journal of Cancer

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“…Our preliminary indications are that DLC-1 expression has an inhibitory effect on in vitro cell growth and in vivo tumorigenicity not only in breast cancer cell lines but also in HCC-derived and prostate carcinoma-derived cell lines. In addition, we have isolated and characterized the mouse DLC-1 gene (Yuan et al, 1999;Durkin et al, 2002) and have constructed a targeting vector for generating mice with a null allele of the gene by homologous recombination. This step should shed additional light on the function and tumor suppressor status of the DLC-1 gene.…”

Section: Discussionmentioning

confidence: 99%

DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity

et al. 2003

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The human DLC-1 (deleted in liver cancer 1) gene was cloned from a primary human hepatocellular carcinoma (HCC) and mapped to the chromosome 8p21-22 region frequently deleted in common human cancers and suspected to harbor tumor suppressor genes. DLC-1 was found to be deleted or downregulated in a significant number of HCCs. We expanded our investigations to other cancers with recurrent deletions of 8p22, and in this study examined alterations of DLC-1 in primary human breast tumors, human breast, colon, and prostate tumor cell lines. Genomic deletion of DLC-1 was observed in 40% of primary breast tumors, whereas reduced or undetectable levels of DLC-1 mRNA were seen in 70% of breast, 70% of colon, and 50% of prostate tumor cell lines To see whether DLC-1 expression affects cell growth and tumorigenicity, two breast carcinoma cell lines lacking the expression of endogenous gene were transfected with the DLC-1 cDNA. In both cell lines, DLC-1 transfection caused significant growth inhibition and reduction of colony formation. Furthermore, introduction of the DLC-1 cDNA abolished the in vivo tumorigenicity in nude mice, suggesting that the DLC-1 gene plays a role in breast cancer by acting as a bona fide tumor suppressor gene.

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“…However, translation initiation at an in‐frame, downstream AUG codon in a better Kozak context would yield a protein of 1083 aa, and there is evidence that the second AUG is the predominant start site (A. Papageorge, X. Qian, D. Lowy, unpublished results). The human DLC‐1 aa sequence is 93% identical to the rat p122RhoGAP [17] and 92% identical to the mouse protein [24, 25]. The rat Dlc1 gene on chromosome 16q12.2 (Rat Genome Database; http://rgd.mcwu.edu) and the mouse Dlc1 gene (formerly called Arhgap7 ) on chromosome 8B1 are located on regions syntenic with human 8p22 and have exon/intron structures nearly identical to that of the human gene, except for the presence of an extra codon in exon 5 of the mouse gene [24, 25].…”

Section: Introductionmentioning

confidence: 99%

DLC‐1:a Rho GTPase‐activating protein and tumour suppressor

Durkin

Yuan

Zhou

et al. 2007

J Cellular Molecular Medi

183

224

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The deleted in liver cancer 1 (DLC-1) gene encodes a GTPase activating protein that acts as a negative regulator of the Rho family of small GTPases. Rho proteins transduce signals that influence cell morphology and physiology, and their aberrant up-regulation is a key factor in the neoplastic process, including metastasis. Since its discovery, compelling evidence has accumulated that demonstrates a role for DLC-1 as a bona fide tumour suppressor gene in different types of human cancer. Loss of DLC-1 expression mediated by genetic and epigenetic mechanisms has been associated with the development of many human cancers, and restoration of DLC-1 expression inhibited the growth of tumour cells in vivo and in vitro. Two closely related genes, DLC-2 and DLC-3, may also be tumour suppressors. This review presents the current status of progress in understanding the biological functions of DLC-1 and its relatives and their roles in neoplasia.

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Assignment<footref rid="foot01"><sup>1</sup></footref> and cloning of mouse <i>Arhgap7</i> to chromosome 8A4–B2, a conserved syntenic region of human chromosome 8p22→p21

Cited by 8 publications

References 3 publications

A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma

A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma

DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity

DLC‐1:a Rho GTPase‐activating protein and tumour suppressor

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