The Proto-oncogene c-myc and c-myb has been shown to be crucial in the development of the hematopoietic system. The changes in the expression of c-myc are concerned the cell proliferation and differentiation, the expression products of which play an important regulatory role in cell growth, differentiation or malignant transformation. The c-myb involves in transcription and affects cell proliferation, differentiation, apoptosis. More recently, the researches on proto-oncogene c-myc, c-myb in hematopoietic regulation have gradually increased along with development of molecular biology, molecular immunology and cell biology. Scientists point out that the directive differentiation of erythroid and megakaryocytic progenitors, and platelet abnormalities all relate to the level of their expressions. The most common thrombocytopathy includes thrombocytopenia, thrombocytosis and so on. The etiology and the mechanism of these diseases are unknown. This article reviews the structure, function and the expression of c-myc and c-myb in platelet diseases and their significance.
Blood Platelet Disorders ; genetics ; metabolism ; Humans ; Proto-Oncogene Proteins c-myb ; genetics ; metabolism ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism

Humans ; Proto-Oncogene Proteins c-met ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism

OBJECTIVEAberrant expression of ten-eleven translocation 1 (TET1) plays a critical role in tumor development and progression. We systematically summarized the latest research progress on the role and mechanisms of TET1 in cancer biology.

DATA SOURCESRelevant articles published in English from 1980 to April 2016 were selected from the PubMed database. The terms "ten-eleven translocation 1," "5mC," "5hmC," "microRNA," "hypoxia," and "embryonic stem cell" were used for the search.

STUDY SELECTIONArticles focusing on the role and mechanism of TET1 in tumor were reviewed, including clinical and basic research articles.

RESULTSTET proteins, the key enzymes converting 5-methylcytosine to 5-hydroxymethylcytosine, play vital roles in DNA demethylation regulation. Recent studies have shown that loss of TET1 is associated with tumorigenesis and can be used as a potential biomarker for cancer therapy, which indicates that TET1 serves as tumor suppressor gene. Moreover, besides its dioxygenase activity, TET1 could induce epithelial-mesenchymal transition and act as a coactivator to regulate gene transcription, such as developmental regulator in embryonic stem cells (ESCs) and hypoxia-responsive gene in cancer. The regulation of TET1 is also correlated with microRNA in a posttranscriptional modification process. Hence, it is complex but critical to comprehend the mechanisms of TET1 in the biology of ESCs and cancer.

CONCLUSIONSTET1 not only serves as a demethylation enzyme but also plays multiple roles during tumorigenesis and progression. More studies should be carried out to elucidate the exact mechanisms of TET1 and its associations with cancer before considering it as a therapeutic tool.

Animals ; Biomarkers ; metabolism ; Carcinogenesis ; genetics ; metabolism ; pathology ; Humans ; MicroRNAs ; genetics ; Mixed Function Oxygenases ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism

Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

This article reviews the specific expression of many proto-oncogenes during male germ cell development. The normal expression of proto-oncogenes plays an important role in the regulation of spermatogonial mitosis, spermatocyte meiosis as well as spermiogenesis and sperm maturation.
Animals ; Gene Expression Regulation ; Male ; Mice ; Proto-Oncogene Proteins ; biosynthesis ; genetics ; Proto-Oncogenes ; genetics ; Spermatocytes ; metabolism ; Transcription, Genetic

BACKGROUNDTransient sublethal ischemia is known as ischemic preconditioning, which enables cells and tissues to survive subsequent prolonged lethal ischemic injury. Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Cbl-b belongs to the Casitas B-lineage lymphoma (Cbl) family, and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioning (OGDPC) in PC12 cells were investigated in the present study.

METHODSOxygen and glucose deprivation (OGD) model in PC12 cells was used in the present study. The 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, nuclear staining with Hoechst 33258, and Western blotting were applied to explore the roles of Cbl-b and PI3K/Akt pathway and the relationship between them in OGDPC in PC12 cells.

RESULTSCell viability was significantly changed by OGD and OGDPC. OGD significantly decreased cell viability compared with the control group (P < 0.05), and preconditioning could rescue this damage was demonstrated by the increase of cell viability (P < 0.05). The expression of Cbl-b was significantly increased after OGD treatment. However, the activation of Akt and GSK3β was greatly inhibited. Preconditioning could inhibit the increase of Cbl-b caused by OGD and increase the activation of Akt and GSK3β. LY294002, a specific inhibitor of PI3K, could effectively inhibit the increase of Akt and GSK3β after preconditioning treatment. It partly inhibited the decrease of Cbl-b expression after preconditioning treatment.

CONCLUSIONUbiquitin ligase Cbl-b and PI3K/Akt pathway are differently involved in OGDPC in PC12 cells.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Animals ; Cell Survival ; Glucose ; deficiency ; Ischemic Preconditioning ; Oxygen ; metabolism ; PC12 Cells ; Phosphatidylinositol 3-Kinase ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Proto-Oncogene Proteins c-cbl ; genetics ; metabolism ; Rats ; Signal Transduction ; physiology

OBJECTIVE: To investigate the molecular mechanism of Wnt5a and Epstein-Barr virus latent membrane protein 1 (LMP1) aberrant expression in the nasopharyngeal carcinogenesis and to estimate if it can act as a molecular marker for nasopharyngeal cancer (NPC). METHODS: Immunohistochemistry combined with previously made tissue microarrays were used to study the expression of Wnt5a and LMP1 in the nasopharyngeal carcinogenesis tissues. We investigated the role of over expression of Wnt5a and LMP1 in the development and progression of NPC and their relation with the clinicopathological features of NPC and whether they could act as molecular markers in benign and malignant NPC. RESULTS: The positive percentage of Wnt5a and LMP1 protein expression in the NPC was significantly increased as compared with that in atypically hyperplastic nasopharyngeal epithelium, hyperplastic nasopharyngeal epithelium and histologically normal nasopharyngeal epithelium (P<0.05, P<0.01, and P<0.01). Wnt5a and LMP1 proteins were significantly higher in atypically hyperplastic nasopharyngeal epithelium than those in the hyperplastic nasopharyngeal epithelium and normal nasopharyngeal epithelium (P<0.05 and P<0.01). The positive expression of Wnt5a and LMP1 proteins in clinical T3 and T4 staged NPC was higher than that in clinical T1 and T2 staged NPC (P<0.01 and P<0.05). The positive expression of Wnt5a protein in the NPC with lymph node metastasis was higher than that in the NPC without lymph node metastasis (P<0.01). The positive percentage of LMP1 protein was significantly increased in non-keratinizing carcinoma compared with undifferentiated carcinoma and keratinizing carcinoma (P<0.05 and P<0.05). The expression of Wnt5a protein in the NPC had significant positive correlation with LMP1 (r=0.354, P<0.001). Combined molecular phenotype of both Wnt5a and LMP1 expression was a good marker to distinguish NPC from non-cancerous nasopharyngeal epithelium. CONCLUSION The expression of Wnt5a and LMP1 protein in the NPC is positively correlated, and both wnt5a and LMP1 protein play important roles in the nasopharyngeal carcinogenesis either together or successively promoting the malignant transformation of nasopharyngeal epithelium and the development and progression of NPC. Both Wnt5a and LMP1 positive expression may act as good markers for NPC differential diagnosis.
Biomarkers, Tumor ; genetics ; metabolism ; Carcinogenesis ; Humans ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; Oncogene Proteins, Viral ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism ; Tissue Array Analysis ; Viral Matrix Proteins ; genetics ; metabolism ; Wnt Proteins ; genetics ; metabolism ; Wnt-5a Protein

This study was aimed to investigate the possible influence of a novel E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70/Hsp70-interacting protein) on biological characteristics of cancer cells. Stable overexpression models in CML K562 cells were established via lipofectamine-mediated wild type CHIP and its TPR or U-box deletion mutants gene transfection. Followed G418 pressure selection, K562-CHIP stable transfected cell clones were obtained by limited dilution. The proliferation status and cell cycle were observed by MTT assay and FACS. The expression of related proteins and morphological changes were detected by Western blot and Wright-Giemsa staining. The results showed that overexpression of wild type CHIP did not inhibit cell proliferation, but slightly increased cell ratio of G(2)/M phase. CHIP gene had no effect on the stability of BCR-ABL kinase protein. HDAC inhibitor FK228-induced BCR-ABL degradation did not enhanced by CHIP. Notably the enlarged cells and abnormal mitotic cells remarkably increased in K562 WT-CHIP cells, indicating that CHIP may involve in the regulation of mitotic process. It is concluded that wild type CHIP induces mitotic abnormity in K562 cells.
Heat-Shock Proteins ; genetics ; metabolism ; Humans ; K562 Cells ; Mitosis ; Nuclear Pore Complex Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism ; Sequence Deletion ; Transfection ; Ubiquitin-Protein Ligases ; genetics ; metabolism

TET2 gene is a member of TET oncogene family. It has been reported as a tumor suppressor gene with important roles in myelopiesis. Recent studies have shown that TET2 protein takes part in demethylation by converting 5-methylcytosine (5-mc) into 5-hydroxymethylcytosine (5-hmc). Somatic TET2 inactivation leads to abnormal myelopiesis and myeloid malignancies. In this review,the structure and function of TET2 and the relationship between TET gene mutation and myeloid malignancies are summarized.
5-Methylcytosine ; analogs & derivatives ; metabolism ; DNA-Binding Proteins ; genetics ; Hematologic Neoplasms ; genetics ; Humans ; Mutation ; Proto-Oncogene Proteins ; genetics

The TET gene family has been found a few years ago. Recent studies indicated that TET2 (TET gene family 2) plays an important role in DNA demethylation, the epigenetic regulation and normal hematopoiesis. TET2 mutation has been discovered in a spectrum of myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and leukemia, which suggest the role of TET2 as a tumor suppressor. In this review the recent results implicating TET2 in hematological malignancies are summarized, including regulatory functions of TET gene epigenetics, TET2 gene and hematopoietic regulation in bone marrow, TET2 gene and hematological disease(MPN, MDS, AML, CMML, lymphoma) and so on.
Bone Marrow ; metabolism ; DNA-Binding Proteins ; genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; Hematologic Diseases ; genetics ; Humans ; Proto-Oncogene Proteins ; genetics