No abstract available.
Cell Cycle Proteins/*metabolism ; Colorectal Neoplasms/diagnosis/*metabolism ; Humans ; Prognosis

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.
Humans ; Transcription Factors/metabolism* ; Nuclear Proteins/metabolism* ; Histones ; Cell Cycle Proteins/metabolism* ; Neoplasms/metabolism* ; Protein Domains

A Kinase Anchor Proteins ; genetics ; metabolism ; Animals ; Cell Cycle Proteins ; genetics ; metabolism ; Humans ; Neoplasms ; genetics ; metabolism

WEE1 is an important factor for histone transcription, chromosome condensation and regulation of cell cycle progression. WEE1 kinase can phosphorylate Cdc2 and down-regulate Cdc2 kinase activity. It can regulate G2 to M phase transition and cell mitosis. It plays a key role in chromosome condensation delay and histone synthesis, suggesting the important functions of WEE1 in the occurrence and development in cancer. At present, a multiple WEE1 inhibitors have been discovered. A great progress has been made in combination of WEE1 inhibitors with DNA damage treatment (chemotherapy or radiotherapy), which makes WEE1 an important target in cancer treatment.
CDC2 Protein Kinase ; metabolism ; Cell Cycle ; Cell Cycle Proteins ; metabolism ; DNA Damage ; Histones ; metabolism ; Humans ; Neoplasms ; metabolism ; Nuclear Proteins ; metabolism ; Phosphorylation ; Protein-Tyrosine Kinases ; metabolism

OBJECTIVETo investigate the role of Sam68 (Src-associated substrate during mitosis 68 kD) in the occurrence and development of colorectal cancer.

METHODSColorectal cancer cell lines with stable Sam68 over-expressing and low Sam68 expression were established to test the effect of Sam68 in the proliferation, invasion, and migration of the cancer cells using colony formation, MTT and Transwell assays.

RESULTSSW480 and Ls174t colorectal cell lines over-expressing Sam68 showed significantly enhanced cell proliferation, invasion and migration (P<0.05). Conversely, the low Sam68 expression in SW620 and HCT116 colorectal cell lines significantly suppressed the cell proliferation, invasion and migration (P<0.05).

CONCLUSIONThe expression of Sam68 can promote the proliferation, invasion and migration of colorectal cancer cells lines in vitro.

Adaptor Proteins, Signal Transducing ; metabolism ; Cell Cycle Proteins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Colorectal Neoplasms ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Humans ; RNA-Binding Proteins ; metabolism

OBJECTIVETo study the expression of hTERT mRNA and Mad1 protein in lung cancer of Gejiu and Xuanwei and normal lung tissue and to investigate their correlations with lung cancer.

METHODSMad1 protein was detected by immunohistochemistry S-P method, and hTERT message RNA (mRNA) was detected by in situ hybridization (ISH) in 40 specimens of lung cancer of Gejiu Tin miners and 20 specimens of lung cancer of Xuanwei peasants and 20 specimens of normal lung tissue. The positive signals were quantitatively analyzed by HPIAS-100.

RESULTSThe positive unit (PU) of Mad1 protein was 16.77 +/- 6.01 in Gejiu Tin Miners lung cancer group, and 19.36 +/- 4.54 in Xuanwei peasant lung cancer group, compared with the normal lung tissue (46.05 +/- 7.26). The difference was highly significant (P < 0.01); The PU of hTERT mRNA was 72.10 +/- 13.07 in Gejiu Tin miners lung cancer group, and 74.20 +/- 15.17 in Xuanwei peasant lung cancer group, which was higher than that in normal tissue group (10.70 +/- 2.21). The difference was significant (P < 0.01). The expression of Mad1 protein was negatively correlated with the expression hTERT mRNA (P < 0.05, r = 0.9881, r = -0.999).

CONCLUSIONReduced hTERT mRNA expression may play an important role in the occurrence of lung cancer. The expression of hTERT mRNA and deletion of Mad1 protein are closely related to pathogenesis of lung cancer.

Cell Cycle Proteins ; metabolism ; China ; Female ; Humans ; Lung ; metabolism ; Lung Neoplasms ; metabolism ; Male ; Mining ; Nuclear Proteins ; metabolism ; Telomerase ; metabolism

The present study is aimed to investigate the toxic effects of andrographolide (Andro) on hepatoma cells and elucidate its preliminary mechanisms. After cells were treated with different concentrations of Andro (0-50 micromol x L(-1)) for 24 h, cell viability was evaluated with 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, after hepatoma cells (Hep3B and HepG2) were treated with different concentrations of Andro (0-30 micromol x L(-1)) for 14 d, the number of colony formation was accounted under microscope. Cell cycle related proteins such as Cdc-2, phosphorylated-Cdc-2, Cyclin B and Cyclin D1 were detected with Western blotting assay and the cell cycle was analyzed by flow cytometry using propidium iodide staining. MTT results showed that Andro induced growth inhibition of hepatoma cells in a concentration-dependent manner but had no significant effects on human normal liver L-02 cells. Andro dramatically decreased the colony formation of hepatoma cells in the concentration-dependent manner. Moreover, Andro induced a decrease of Hep3B cells at the G0-G1 phase and a concomitant accumulation of cells at G2-M phase. At the molecular level, Western blotting results showed that Andro decreased the expression of Cdc-2, phosphorylated-Cdc-2, Cyclin D1 and Cyclin B proteins in a time-dependent manner, which are all cell cycle related proteins. Taken together, the results demonstrated that Andro specifically inhibited the growth of hepatoma cells and cellular cell cycle related proteins were possibly involved in this process.
Carcinoma, Hepatocellular ; metabolism ; Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; Cell Survival ; drug effects ; Diterpenes ; pharmacology ; Humans ; Liver Neoplasms ; metabolism

OBJECTIVE: To investigate the regulatory role of Musashi-1 (MSI1) in the proliferation and growth of hepatocellular carcinoma (HCC) cells. METHODS: We examined the expression of MSI1 in HCC and paired adjacent tissues from 24 patients using immunohistochemistry and Western blotting. A MSI1-expressing vector was constructed and stably transfected into HepG2 cells, and short hairpin RNAs (shRNAs) that targeted MSI1 mRNA were ligated into the vector and stably transfected in Huh7 cells. The effects of MSI1 overexpression and silencing on the proliferation, viability and cell cycle of HepG2 cells were investigated using flow cytometry or MTT assay. The expressions of PCNA, cyclin D1, APC and β-catenin in the HCC cells were detected with Western blotting. RESULTS: MSI1 expression was significantly up-regulated in HCC tissues as compared with that in the adjacent tissues. Overexpression of MSI1 in HepG2 cells resulted in significantly enhanced cell growth ( < 0.01) and significantly reduced G0/G1 phase cells from (58.42±3.18)% to (40.67±1.22)% and increased S phase cells from (28.51± 1.93)% to (40.06±1.92)% ( < 0.01), causing also increases in the expressions of PCNA and Cyclin D1. Knockdown of MSI1 in Huh7 cells obviously inhibited the cell growth and caused cell cycle arrest at the G1/S phase ( < 0.01) with reduced protein expressions of PCNA and cyclin D1. Overexpression of MSI1 in HepG2 cells also down-regulated the expression of APC and up-regulated the expression of β-catenin protein, while MSI1 knockdown caused reverse changes in Huh7 cells. CONCLUSIONS MSI1 promotes the progression of HCC through positive modulation of cell growth and cell cycle the Wnt/β-catenin pathway.
Carcinoma, Hepatocellular ; Cell Cycle ; Cell Proliferation ; Hep G2 Cells ; Humans ; Liver Neoplasms ; Nerve Tissue Proteins ; metabolism ; RNA-Binding Proteins ; metabolism

OBJECTIVETo explore the inhibitory effect of norcantharidin (NCTD) on the expression of DNA replication initiation protein Cdc6 in cancer cells.

METHODSMTT assay was performed to detect the inhibitory effect on different cancer cell lines, including HeLa, HepG2, Jurkat and Ramos cells. The effect of NCTD on Cdc6 protein level was detected by Western blotting, and BrdU incorporation assay was used to evaluate the DNA replication of the cells.

RESULTSNCTD significantly inhibited the proliferation of the cells and caused degradation of Cdc6 protein to result in the inhibition of the DNA replication of the cells shown by BrdU incorporation assay.

CONCLUSIONNCTD can induce the degradation of Cdc6 in cancer cells to produce an anti-cancer effect.

Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; DNA Replication ; drug effects ; Humans ; Nuclear Proteins ; metabolism

AIMTo establish a HSP90 highly expressing cell line and study the effect of high level of HSP90 on cell stress response.

METHODSThe recombined plasmid pSmycHSP, which contained the full length DNA coding for human HSP90 B, was introduced into mouse fibroblast cell line NIH-3T3 by electroporation after being subcloned, purified and identified by limited enzyme digestion. After screened by G418, the positive clones were selected and identified by immunocytochemistry and Western-blotting. Contrasted with NIH-3T3 cells transfected with empty plasmid, the effect of high-level HSP90 on cell proliferation and cell cycle was analyzed by MTT method and flow cytometry.

RESULTSThe rising level of HSP90 was shown by immunocytochemistry and Western-blotting. Compared with control, the growth of HSP90 highly expressing cell line slowed down and the DNA content of S phase was lower.

CONCLUSIONThe NIH-3T3 derived cell line, which stably expressed high level of HSP90 was established. The effect of high-level HSP90 on cell proliferation was to retard cell growth by affecting cell cycle.

Animals ; Cell Cycle ; Cell Proliferation ; HSP90 Heat-Shock Proteins ; metabolism ; Mice ; NIH 3T3 Cells