As a pro-apoptotic factor, prostate apoptosis response protein 4 (par-4) was first found in the male hormone-dependent prostate cells (AT-3). Endogenous Par-4 sensitizes cancer cells to apoptotic stimuli, but exogenous Par-4 selectively induces apoptosis in cancer cells, and these activities depends on the structure of its core domain SAC. Par-4 and SAC can specifically induce apoptosis of cancer cells but not of normal cells, and are therefore potential anti-cancer drugs. In this review we summarize the discovery, structure, and function of par-4, and its intracellular signaling pathways, then discuss the application prospects of Par-4 and SAC in the clinical treatment of cancer and the problems in its research and clinical applications.
Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Humans ; Tumor Suppressor Proteins

Glioblastoma ; genetics ; metabolism ; Humans ; Mutation ; Oncogene Proteins ; genetics ; metabolism ; 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*

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

To investigate the relationship between the expression of RASSF1A protein and promoter hypermethylation of RASSF1A gene, RASSF1A protein expression was measured by Western blotting in 10 specimens of normal bladder tissues and 23 specimens of bladder transitional cell carcinoma (BTCC). The promoter methylation in BTCC and normal bladder tissues was detected by methylation-specific PCR (MSP). The results showed that the expression level of RASSF1A protein was significantly lower in BTCC tissues than that in normal bladder tissues. However, it was not correlated with its clinical stages and pathological grades. The frequency of promoter methylation of RASSF1A gene was higher in BTCC tissues than that in normal bladder tissues. In 14 patients with the aberrant promoter methylation, 13 showed loss or low expression of RASSF1A protein. It is concluded that RASSF1A gene promoter methylation may contribute to the low level or loss of RASSF1A protein expression, the inactivation of RASSF1A gene and the genesis of BTCC. But, it may bear no correlation with its clinical stages and pathological grades.
Blotting, Western ; Carcinoma, Transitional Cell/metabolism ; DNA Methylation ; DNA Primers/chemistry ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Promoter Regions, Genetic ; Tumor Suppressor Proteins/*biosynthesis ; Tumor Suppressor Proteins/*genetics ; Urinary Bladder Neoplasms/*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

OBJECTIVETo search for a new diagnostic biomarker for prostate cancer by comparing the differences in the expressions of netrin-1 and UNC5B in prostate cancer cells with different invasive abilities.

METHODSWe examined the expressions of netrin-1 and UNC5B in five prostate cancer cell lines DU145, 22RV1, PC3, PC3M and RWPE-1 using RT-PCR and Western blot, and positioned the ligands netrin-1 and its receptor UNC5B in the prostate cancer cells by immunofluorescence.

RESULTSBoth netrin-1 and UNC5B were expressed in the prostate cancer cells, and the expression of netrin-1 was significantly increased in highly invasive cells (P < 0.05), while that of UNC5B in RWPE-1 (normal) cells (P < 0.05).

CONCLUSIONThe expressions of netrin-1 and UNC5B are closely related to the infiltration and progression of prostate cancer, and expected to be as potential biomarkers for predicting the malignancy degree of prostate cancer.

Biomarkers, Tumor ; metabolism ; Cell Line, Tumor ; Humans ; Male ; Nerve Growth Factors ; metabolism ; Netrin-1 ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, Cell Surface ; metabolism ; Tumor Suppressor Proteins ; metabolism

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

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

BACKGROUNDP53 is one of the most studied tumor suppressors in the cancer research, and over 50% of human tumors carry P53 mutations. MDM-2 is amplified and/or overexpressed in a variety of human tumors of diverse tissue origin. The aim of this study was to examine the expression of P53 protein and MDM-2 protein in gliomas, and to investigate the relationship between the expression of the two proteins and the histopathological grades of glioma. The relationship between MDM-2 protein expression and P53 protein expression was also analyzed.

METHODSThe expression of P53 protein and MDM-2 protein was immunohistochemically detected using monoclonal antibodies in 242 paraffin embedded tissues, including 30 normal brain tissues from patients with craniocerebral injury and 212 tissues from patients with primary glioma (grade I - II group: 5 cases of grade I, 119 cases of grade II; and grade III--IV group: 53 cases of grade III, and 35 cases of grade IV).

RESULTSThe P53 positive rate was significantly higher in the glioma groups than in the control group (P < 0.0001). The P53 positive rate was significantly higher in glioma tissues of grade III - IV than in glioma tissues of grade I - II group (P = 0.001). The MDM-2 positive rate was significantly higher in glioma groups than in the control group (P < 0.0001). There was no significant difference in the MDM-2 positive rate between the two glioma groups (P = 0.936). The expression of P53 protein was not related to expression of MDM-2 protein (P = 0.069)

CONCLUSIONSOverexpression of P53 protein might be related to the occurrence and progression of glioma. Overexpression of MDM-2 protein may play an important role in glioma tumorigenesis, but may not be involved in glioma progression. The overexpression of MDM-2 protein was an early event in malignant transformation of glioma. MDM-2 may be a key player in glioma in its own right.

Glioma ; metabolism ; pathology ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Proto-Oncogene Proteins c-mdm2 ; metabolism ; Tumor Suppressor Protein p53 ; metabolism