A Newly Identified Member of the Tumor Necrosis Factor Receptor Superfamily with a Wide Tissue Distribution and Involvement in Lymphocyte Activation

Kwon, Byoung S.; Tan, K. B.; Ni, Jian; Kwi-Ok-Oh, Zang H Lee; Kim, Kack K.; Kim, Young-J.; Wang, Sa; Gentz, Reiner; Yu, Guoliang; Harrop, Jeremy; Lyn, Sally D.; Silverman, Carol; Porter, Terence G.; Truneh, Alem; Young, Peter R.

doi:10.1074/jbc.272.22.14272

Cited by 278 publications

(200 citation statements)

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“…A number of potential candidate genes are located in the distal region of 1p, such as the Zinc Finger ZFM60, the developmental regulator gene Pax7, the helix-loop-helix protein Heir-1, the cell cycle regulator p58, the transcription factor E2F-2, TR2 gene, and p18 cyclindependent kinase inhibitor gene. Some of the genes in this region, such as p18 cyclin-dependent kinase inhibitor gene, have been ruled out as candidate genes; however, the role of many of these candidate genes still remains to be elucidated (4,6,12). p73 gene, with a significant homology to p53, is located just at the D1S468 locus of 1p36.3 (13).…”

Section: Discussionmentioning

confidence: 99%

Frequent Loss of Heterozygosity at 1p36.3 and p73 Abnormality in Parathyroid Adenomas

et al. 2001

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Although 1p is one of the most common loci showing loss of heterozygosity (LOH) in primary parathyroid adenoma, fine mapping has not been previously examined. In this study, we analyzed LOH in 32 primary parathyroid adenomas using five microsatellite markers at 1p36 (proximal-D1S507-D1S450-D1S2893-D1S468-D1S243-distal). All cases were heterozygous for at least one marker. The frequency of LOH varied from 41.2% (D1S468) to 7.1% (D1S507) among the different markers. LOH was detected consistently in a group of nine adenomas (28.1%, 9/32). A single region (7 cM) showing a consistent LOH at 1p36.3 was obtained that was flanked distally by D1S468 and proximally by D1S2893. Because the p73 gene is localized within this region and acts as a tumor suppressor gene, we examined the possible involvement of p73 in the development of parathyroid tumor. Allelic loss of p73 was identified in four adenomas (25%, 4/16 informative cases) that were all from the group of the nine adenomas with LOH, but somatic mutation was not detected in the remaining allele. At the StyI polymorphism of Exon 2, four of the six adenomas with LOH at 1p36 were heterozygous and expressed the GC allele. Of the six heterozygous adenomas without LOH, 4 showed biallelic and 2 monoallelic expressions (GC allele). All adenomas mainly expressed the p73␣ isoform. p73 protein was observed in five of the six adenomas with LOH and in two of the six adenomas without LOH. There were no differences in p73 protein levels between the samples with and without LOH. In conclusion, a candidate gene for parathyroid tumorigenesis is present within a 7-cM region at 1p36.3, however p73 is unlikely to be the target of the LOH at 1p36.3. KEY WORDS: 1p36, Hyperparathyroidism, Loss of heterozygosity, Parathyroid neoplasia, p73. Mod Pathol 2001;14(4):273-278Parathyroid adenoma is one of the most common endocrine tumors, characterized by excessive secretion of parathyroid hormone (PTH) and enlargement of mostly one parathyroid gland. The molecular mechanism of parathyroid tumorigenesis is still poorly understood (1). MEN 1 gene abnormality has been found in only about 20% of the sporadic parathyroid adenomas. Cyclin D1/PTH gene rearrangement seems to be involved only in a small subset of these tumors, and p53 gene mutations also appear to be rare. To localize the gene responsible for parathyroid tumorigenesis, loss of heterozygosity (LOH) has been analyzed in various loci, and different frequencies of LOH have been identified (2, 3

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Section: Discussionmentioning

confidence: 99%

Frequent Loss of Heterozygosity at 1p36.3 and p73 Abnormality in Parathyroid Adenomas

et al. 2001

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“…This was initially demonstrated by experiments in which immobilized recombinant LIGHT promoted T cell proliferation in the presence of anti-CD3 [5]. Reagents that blocked HVEM, like anti-HVEM antibody [6] or HVEM-Ig [83], reduced T cell expansion and their cytokine production in the same setting. This is consistent with the later findings that CD8 + T cell activation, expansion and CTL activity are defective in LIGHT-deficient mice [84][85][86].…”

Section: Light Sustains Effector T Cell Functions At the Tumor Sitementioning

confidence: 99%

“…LIGHT uniquely binds to two functional receptors, HVEM and lymphotoxin β receptor (LTβR) [2,4], which are TNF receptor superfamily members (TNFRSF) that have distinct expression patterns. HVEM is broadly expressed on hematopoietic cells including T cells, natural killer (NK) cells, and monocytes [5,6]. Conversely, LTβR is mainly expressed on nonhematopoietic cells such as stromal cells [7] and some monocyte cell lines [8].…”

Section: Introductionmentioning

confidence: 99%

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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Metastastic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor superfamily member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells, NK cells, naïve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin β receptor (LTβR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy.

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“…The cellular receptors (or appropriate species-specific homologues) responsible for virion docking and uptake have been cloned, including the herpesvirus entry mediator A (HveA; formerly HVEM) and nectin-1 (formerly HveC), and, not surprisingly, have been shown to be nearly ubiquitously expressed. [1][2][3][4] Intracellular transport of the viral genome to the nucleus leads to a highly coordinated cascade of viral gene expression. Based upon cellular/ molecular signals that gauge the status of the host cell environment, HSV infection can progress via two distinct paths: one that involves active viral gene expression to produce new virions (lytic phase) or another that involves an abolition of a majority of viral gene expression (latent phase).…”

Section: Introductionmentioning

confidence: 99%

Immune responses to replication-defective HSV-1 type vectors within the CNS: implications for gene therapy

2003

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A Newly Identified Member of the Tumor Necrosis Factor Receptor Superfamily with a Wide Tissue Distribution and Involvement in Lymphocyte Activation

Cited by 278 publications

References 50 publications

Frequent Loss of Heterozygosity at 1p36.3 and p73 Abnormality in Parathyroid Adenomas

Frequent Loss of Heterozygosity at 1p36.3 and p73 Abnormality in Parathyroid Adenomas

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Immune responses to replication-defective HSV-1 type vectors within the CNS: implications for gene therapy

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