Glioblastoma ; genetics ; metabolism ; Humans ; Mutation ; Oncogene Proteins ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

CKLF-like MARVEL transmembrane domain containing member(CMTM)is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM5 belongs to this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily(TM4SF). CMTM5 is broadly expressed in normal adult and fetal human tissues, but is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM5 may inhibit the proliferation, migration, and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear, CMTM5 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM5 may be a new target in the gene therapies for tumors, while further studies on CMTM5 and its anti-tumor mechanisms are warranted.
Chemokines ; genetics ; metabolism ; Humans ; MARVEL Domain-Containing Proteins ; genetics ; metabolism ; Neoplasms ; genetics ; metabolism ; Signal Transduction ; Tumor Suppressor Proteins ; genetics ; metabolism

The gastrointestinal tract is the largest digestive organ and the largest immune organ and detoxification organ, which is vital to the health of the body. Drosophila is a classic model organism, and its gut is highly similar to mammalian gut in terms of cell composition and genetic regulation, therefore can be used as a good model for studying gut development. target of rapmaycin complex 1 (TORC1) is a key factor regulating cellular metabolism. Nprl2 inhibits TORC1 activity by reducing Rag GTPase activity. Previous studies have found that nprl2 mutated Drosophila showed aging-related phenotypes such as enlarged foregastric and reduced lifespan, which were caused by over-activation of TORC1. In order to explore the role of Rag GTPase in the developmental defects of the gut of nprl2 mutated Drosophila, we used genetic hybridization combined with immunofluorescence to study the intestinal morphology and intestinal cell composition of RagA knockdown and nprl2 mutated Drosophila. The results showed that RagA knockdown alone could induce intestinal thickening and forestomach enlargement, suggesting that RagA also plays an important role in intestinal development. Knockdown of RagA rescued the phenotype of intestinal thinning and decreased secretory cells in nprl2 mutants, suggesting that Nprl2 may regulate the differentiation and morphology of intestinal cells by acting on RagA. Knockdown of RagA did not rescue the enlarged forestomach phenotype in nprl2 mutants, suggesting that Nprl2 may regulate forestomach development and intestinal digestive function through a mechanism independent of Rag GTPase.
Animals ; Drosophila/genetics* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mammals/metabolism* ; Carrier Proteins ; Tumor Suppressor Proteins/metabolism* ; Drosophila Proteins/genetics*

Timely cell cycle regulation is conducted by sequential activation of a family of serine-threonine kinases called cycle dependent kinases (CDKs). Tight CDK regulation involves cyclin dependent kinase inhibitors (CKIs) which ensure the correct timing of CDK activation in different phases of the cell cycle. One CKI of importance is p27(KIP1). The regulation and cellular localization of p27(KIP1) can result in biologically contradicting roles when found in the nucleus or cytoplasm of both normal and tumor cells. The p27(KIP1) protein is mainly regulated by proteasomal degradation and its downregulation is often correlated with poor prognosis in several types of human cancers. The protein can also be functionally inactivated by cytoplasmic localization or by phosphorylation. The p27(KIP1) protein is an unconventional tumor suppressor because mutation of its gene is extremely rare in tumors, implying the normal function of the protein is deranged during tumor development. While the tumor suppressor function is mediated by p27(KIP1)'s inhibitory interactions with the cyclin/CDK complexes, its oncogenic function is cyclin/CDK independent, and in many cases correlates with cytoplasmic localization. Here we review the basic features and novel aspects of the p27(KIP1) protein, which displays genetically separable tumor suppressing and oncogenic functions.
Animals ; Cyclin-Dependent Kinases/genetics/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mutation ; Neoplasms/genetics/*metabolism ; Phosphorylation/genetics ; Protein Transport/genetics ; Tumor Suppressor Proteins/genetics/*metabolism

OBJECTIVETo study the over-expression of mutant p53 protein in non-mucinous adenocarcinoma in-situ (NMAIS) and invasive adenocarcinoma, NOS of lung.

METHODSImmunohistochemical study for p53 protein was performed on 17 cases of NMAIS and 70 cases of invasive adenocarcinoma, NOS of lung. The difference in p53 over-expression between the two tumor subtypes was analyzed.

RESULTSThe over-expression of mutant p53 protein was observed in 0 case (0%) of NMAIS and 37 cases (52.9%) of invasive adenocarcinoma, NOS of lung. The difference was of statistical significance (P = 0.000).

CONCLUSIONMutant p53 protein over-expression may play a role in the progression of NMAIS to invasive adenocarcinoma, NOS.

Adenocarcinoma ; metabolism ; Adenocarcinoma in Situ ; metabolism ; Humans ; Immunohistochemistry ; Mutant Proteins ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism

MicroRNA-21 (miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors. Through functional suppression, miR-21 is implicated in practically every walk of oncogenic life: the promotion of cell proliferation, invasion and metastasis, genome instability and mutation, inflammation, replicative immortalization, abnormal metabolism, angiogenesis, and evading apoptosis, immune destruction, and growth suppressors. In particular, miR-21 is strongly involved in apoptosis. In this article, we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis. This suggests that miR-21 is an oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Genes, Tumor Suppressor ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasms ; genetics ; metabolism ; pathology ; PTEN Phosphohydrolase ; metabolism ; RNA-Binding Proteins ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVE: To investigate the ING1 gene mutation status in human laryngeal squamous cell carcinoma(LSCC), and the association of p33(ING1b) protein expression with p53 protein expression. METHOD: DNA of LSCC tissue was extracted, and nucleotide of the second exon was amplified and sequenced to determine the chromosome status. The p23(ING1b) and p53 protein expression were detected by immunohistochemistry and the association between them were analyzed. RESULT: No mutation was detected in ING1 gene, but a single polymorphism from GGG to AGG at codon 170 of ING1 gene was found in 2 of the 25 LSCC tissues. The immunohistochemical analysis showed that 4 had positive p33(ING1b) expression. No association was found between p33(ING1b) expression and LSCC clinical features, or between p53 and clinical features. However, significant difference was found between p33(ING1b) and p53 expression. p33(ING1b) tended to be negative in p53 expression positive tissue. CONCLUSION ING1 gene mutation appears rare in LSCC. In normal physical condition, p33(ING1b) may play a synergistic effect with p53 protein.
Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Female ; Genes, Regulator ; Humans ; Inhibitor of Growth Protein 1 ; Intracellular Signaling Peptides and Proteins ; genetics ; Laryngeal Neoplasms ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Tumor Suppressor Protein p53 ; metabolism ; Tumor Suppressor Proteins ; genetics

Oncogene and antioncogene play contrary effects on the cell growth and proliferation controlling process, and cancer occurs when the presence of imbalance expression between them. That means there is yin-yang relationship between oncogene (yang) and antioncogene (yin), and also inside both of them. Taking the oncogene myc and antioncogene p53 for example, the yin gene p53 acts, in the yin side, to promote cell apoptosis and inhibit cell growth, while in the yang side, it facilitates for repairing the injured DNA to keep cell survival; the yang gene myc, promoting cell growth and proliferation in the yang side and inducing cell apoptosis in the yin side. To elucidate the yin-yang reactions between oncogene and antioncogene would be of important significance in the all-round and profound research of cancer.
Genes, Tumor Suppressor ; Humans ; Medicine, Chinese Traditional ; Neoplasms ; genetics ; Oncogenes ; genetics ; Proto-Oncogene Proteins c-myc ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; Yin-Yang

OBJECTIVE: To explore the correlation between histone H3-K9 methylation, DNA methylation and expression of carcinoma suppressor gene MGMT in laryngeal carcinoma Hep-2 cell line. METHOD: 5-Aza-dC was used to deal with Hep-2 cell cultured in vitro. ChIP, MSP and Realtime-PCR were used to detect H3-K9 methylation, DNA methylation, of MGMT gene promoter region and MGMT gene expression before and after treatment with drugs. RESULT: (1) In Hep-2 cell line, gene MGMT was characterized by DNA methylation and histone H3-K9 hypermethylation. (2) 5-Aza-dC was able to reduce H3-K9 methylation of MGMT gene histone in Hep-2 cell line, 5-Aza-dC was able to reverse DNA methylation of MGMT gene histone in Hep-2 cell line, 5-Aza-dC was able to upregulate the down-regulated gene expression of tumor suppressor genes MGMT. CONCLUSION Promoter methylation of cancer suppressor gene MGMT may induce the gene inactivity. DNA methylation may increase H3-K9 methylation. 5-Aza-dC can reduce H3-K9 methylation of tumor suppressor gene MGMT histone by reversing DNA methylation of tumor suppressor gene MGMT, and then the expression of tumor suppressor genes is increased and tumor development is inhibited.
Cell Line, Tumor ; DNA Methylation ; DNA Modification Methylases ; genetics ; metabolism ; DNA Repair Enzymes ; genetics ; metabolism ; Genes, Tumor Suppressor ; Histones ; metabolism ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; pathology ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo study the effects of anti-oncogene WWOX on cell growth of cholangiocarcinoma.

METHODSThe expression of WWOX protein was detected with immunohistochemical method-SP in 54 patients with cholangiocarcinoma from July 2005 to May 2010 and 12 samples of normal bile duct tissues. The recombinant WWOX eukaryotic expression plasmid was introduced into RBE cells by liposome-mediated transfection and positive cell clones were selected and amplified. The mRNA and protein expressions in RBE cells stably transfected with WWOX were investigated by quantitative RT-PCR and Western Blot before and after transfection. Cell proliferation was tested by MTT, cell apoptosis was assessed by FCM, the alteration of mitochondria membrane potential (ΔΨm) was detected by JC-1 staining method, cell invasion was determined by Transwell chamber assay. The expression change of bcl-2, bax, FasL, caspase-3 mRNA and protein was detected by quantitative RT-PCR and Western Blot.

RESULTSThe expression of WWOX protein was significantly lower in cholangiocarcinoma than that in normal bile duct tissues and loss of WWOX protein expression was found in 40.7% of cholangiocarcinoma specimens (P < 0.05). RBE cells with stable transfection of WWOX were established. Quantitative RT-PCR showed that the expression of WWOX mRNA was significantly enhanced and Western Blot demonstrated that WWOX protein expression was markedly increased. MTT showed that WWOX gene transfection significantly decreased the proliferation of RBE cells (P < 0.05). FCM analysis showed that the apoptosis rate after transfection was significantly promoted [(1.1 ± 0.6)% vs. (1.7 ± 0.5)% vs. (35.2 ± 4.4)%, P < 0.01], JC-1 staining method indicated that the experimental group was loss of ΔΨm [(12.6 ± 1.9)% vs. (13.6 ± 1.8)% vs. (48.7 ± 2.9)%, P < 0.01], transwell chamber assay showed that the number of transfected cells that passed the transwell membrane was significantly less than those of control groups (77 ± 6 vs. 72 ± 8 vs. 48 ± 6, P < 0.01). Quantitative RT-PCR and Western blotting showed that the expression of bcl-2 mRNA and protein was markedly decreased and the expression of bax, caspase-3 were significantly increased. There was no significant change in the expression of FasL.

CONCLUSIONWWOX exerts its antitumor effect against proliferation through inducing cell apoptosis in cholangiocarcinoma.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cholangiocarcinoma ; genetics ; metabolism ; pathology ; Genetic Vectors ; Humans ; Oxidoreductases ; genetics ; metabolism ; Plasmids ; genetics ; Transfection ; Tumor Suppressor Proteins ; genetics ; metabolism ; WW Domain-Containing Oxidoreductase