TC2N: A Novel Vital Oncogene or Tumor Suppressor Gene In Cancers

Several C2 domain-containing proteins play key roles in tumorigenesis, signal transduction, and mediating protein–protein interactions. Tandem C2 domains nuclear protein (TC2N) is a tandem C2 domain-containing protein that is differentially expressed in several types of cancers and is closely associated with tumorigenesis and tumor progression. Notably, TC2N has been identified as an oncogene in lung and gastric cancer but as a tumor suppressor gene in breast cancer. Recently, a large number of tumor-associated antigens (TAAs), such as heat shock proteins, alpha-fetoprotein, and carcinoembryonic antigen, have been identified in a variety of malignant tumors. Differences in the expression levels of TAAs between cancer cells and normal cells have led to these antigens being investigated as diagnostic and prognostic biomarkers and as novel targets in cancer treatment. In this review, we summarize the clinical characteristics of TC2N-positive cancers and potential mechanisms of action of TC2N in the occurrence and development of specific cancers. This article provides an exploration of TC2N as a potential target for the diagnosis and treatment of different types of cancers.

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Loss of heterozygosity at the mannose 6-phosphate/insulin-like growth factor 2 receptor locus: a frequent but late event in adrenocortical tumorigenesis

Acta Endocrinologica ◽

10.1530/eje.0.1440163 ◽

2001 ◽

pp. 163-168 ◽

Cited By ~ 25

Author(s):

S Leboulleux ◽

V Gaston ◽

N Boulle ◽

Y Le Bouc ◽

C Gicquel

Keyword(s):

Growth Factor ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Loss Of Heterozygosity ◽

Malignant Tumors ◽

Suppressor Gene ◽

Benign Tumors ◽

Adrenocortical Tumors ◽

Frequent Event ◽

Mannose 6 Phosphate

OBJECTIVE: Recent studies have pointed to the role of the IGF system in adrenocortical tumorigenesis. The IGF-II gene is overexpressed in malignant adrenocortical tumors and its proliferative effects are mediated by the type-1 IGF receptor (IGF1R). The mannose 6-phosphate/IGF2 receptor (M6P/IGF2R) plays a key role in regulating cell growth, by ensuring the clearance and inactivation of IGF-II and facilitating activation of the growth inhibitor, transforming growth factor beta (TGFbeta1). The M6P/IGF2R has been implicated as a tumor suppressor gene in various human tumors. METHODS: The purpose of this study was to determine if the M6P/IGF2R is involved in adrenal tumorigenesis. Two polymorphisms in the 3' untranslated region of M6P/IGF2R were used to screen a large series of 76 sporadic adrenocortical tumors for loss of heterozygosity (LOH) by PCR amplification of DNA. Tumors were classified into three groups based on pathological features: benign tumors (n=25), suspect tumors (n=22) and malignant tumors (n=29). RESULTS: LOH at the M6P/IGF2R locus was detected in 15 of 57 (26%) informative tumors and was more frequent in malignant tumors (58%) than in benign and suspect tumors (9 and 13% respectively). CONCLUSION: These findings provide evidence that LOH at the M6P/IGF2R locus is a frequent event in adrenocortical tumors and support the hypothesis that it may function as a tumor suppressor gene in adrenocortical tumorigenesis.

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FHITDoubts are Clear Now

The Scientific World JOURNAL ◽

10.1100/tsw.2010.110 ◽

2010 ◽

Vol 10 ◽

pp. 1142-1151 ◽

Cited By ~ 19

Author(s):

Anjilna Wali

Keyword(s):

Tumor Suppressor ◽

Cell Line ◽

Tumor Suppressor Gene ◽

Promoter Region ◽

Suppressor Gene ◽

Genetic Alterations ◽

Chromosome 3 ◽

Loss Of Function ◽

Methylation Analysis ◽

Different Types

The fragile histidine triad (FHIT) gene is a bonafide tumor-suppressor gene present on the short arm of chromosome 3 and its loss of function has been evaluated in different types of cancers. Loss of heterozygosity at various sections of theFHITgene and the methylation analysis of the promoter region showed that it is one of the important and preliminary genetic alterations in the cell, and its restoration in the cell line or nude mice suppresses tumorigenicity. Current research on theFHITgene has depicted that Fhit interacts with different proteins through different pathways in the nucleus, mitochondria, and cytoplasm, directing the cell to apoptosis.

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The NF2 Tumor Suppressor Gene Product, Merlin, Inhibits Cell Proliferation and Cell Cycle Progression by Repressing Cyclin D1 Expression

Molecular and Cellular Biology ◽

10.1128/mcb.25.6.2384-2394.2005 ◽

2005 ◽

Vol 25 (6) ◽

pp. 2384-2394 ◽

Cited By ~ 119

Author(s):

Guang-Hui Xiao ◽

Ryan Gallagher ◽

Justin Shetler ◽

Kristine Skele ◽

Deborah A. Altomare ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Tumor Suppressor ◽

Cyclin D1 ◽

Tumor Suppressor Gene ◽

Promoter Activity ◽

Cell Cycle Progression ◽

Malignant Tumors ◽

Suppressor Gene ◽

Cycle Progression

ABSTRACT Inactivation of the NF2 tumor suppressor gene has been observed in certain benign and malignant tumors. Recent studies have demonstrated that merlin, the product of the NF2 gene, is regulated by Rac/PAK signaling. However, the mechanism by which merlin acts as a tumor suppressor has remained obscure. In this report, we show that adenovirus-mediated expression of merlin in NF2-deficient tumor cells inhibits cell proliferation and arrests cells at G1 phase, concomitant with decreased expression of cyclin D1, inhibition of CDK4 activity, and dephosphorylation of pRB. The effect of merlin on cell cycle progression was partially overridden by ectopic expression of cyclin D1. RNA interference experiments showed that silencing of the endogenous NF2 gene results in upregulation of cyclin D1 and S-phase entry. Furthermore, PAK1-stimulated cyclin D1 promoter activity was repressed by cotransfection of NF2, and PAK activity was inhibited by expression of merlin. Interestingly, the S518A mutant form of merlin, which is refractory to phosphorylation by PAK, was more efficient than the wild-type protein in inhibiting cell cycle progression and in repressing cyclin D1 promoter activity. Collectively, our data indicate that merlin exerts its antiproliferative effect, at least in part, via repression of PAK-induced cyclin D1 expression, suggesting a unifying mechanism by which merlin inactivation might contribute to the overgrowth seen in both noninvasive and malignant tumors.

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