Cell Cycle Proteins ; Microtubule-Associated Proteins

The cell cycle is the set of events that is responsible for the duplication of the cells. Recent studies indicate that cell cycle regulatory proteins, mainly the cyclins and cyclin-related genes, can be critical targets during oncogenesis. The genes and gene products normally control specific events in the cell cycles, particularly during the late G1 and early S phase and G2/M phase. A large body of date implicates cyclins in oncogenesis. The first evidence came from human cyclin A in oncogenesis. Cyclin A is expressed from the late G1 phase through the M-phase of the cell cycle. Cyclin A is known as positive regulator of cell cycle and participates in the tumorigenesis. Overexpression of cyclin A has been reported in several cancers. Ki-67 is a nuclear protein expressed during the cell cycle except in Go. The labeling index of Ki-67 in the tumor cell nuclei has been used as a good prognostic factor. In this study, we compared labeling index of cyclin A and Ki-67 to assess the feasibility between them with 30 cases of cervical intraepithelial neoplasia(CIN) and 20 cases of invasive squamous cell carcinoma(SCC)by immunohistochemistry. The results were as follow; 1. Cyclin A expressed in normal parabasal cells and their labeling index was 0.8+/-0.4%, while in CIN and invasive SCC 65.5+/-9.4% and 86.5+/-12.3% respectively. Ki-67 expressed in normal parabasal cells as 1.3+/-0.7% while in CIN and invasive SCC as 77.8+/-12.9% and 92.2+/-17.6% respectively. 2. In CIN, the expression of cyclin A increased according to the grades of the CIN as 32.5+/-5.7%, 75.8+/-9.0%, and 83.2+/-13.4% in CIN I, II and III respectively. The expression of the Ki-67 also increased according to the grades of the CIN as 51.8+/-9.8%, 87.9+/-11.3%, and 93.6+/-17.5% respectively in CIN I, II and III. 3. There was no differences of cyclin A and Ki-67 expressions according to the histologic types of invasive SCC. Above results suggests that the cyclin A labeling index could be used as a marker of tumor progression in the uterine cervical carcinoma as Ki-67.
Carcinogenesis ; Cell Cycle ; Cell Cycle Proteins ; Cell Nucleus ; Cyclin A* ; Cyclins* ; G1 Phase ; Humans ; Immunohistochemistry ; Nuclear Proteins ; S Phase

Gingival fibroblasts are major cellular component of gingiva. However, the molecular mechanisms of senescence of human gingival fibroblasts are unknown. Human fibroblasts undergo replicative senescence in vitro after a limited number of population doublings. A reduced rate of proliferation is a prominent phenomenon observed in senescent fibroblasts. This phenomenon is happened with cell cycle arrest that was controled by cell cycle regulatory proteins. The purpose of present study was to investigate the effect of replicative senescence on cell cycle progression and to find out its molecular mechanisms in human gingival fibroblasts. Replicative senescence of gingival fibroblasts were induced by subsequent cultures that were repeated up to 18 passage. In the present study, I examined change of cell proliferation, cell activity, cell viability and cell cycle progression during the replicative process. Also, I examined expression of cell cycle regulatory proteins which was estimated by western blot analysis. Cell proliferation, cell activity and cell viability of gingival fibroblasts were notably decreased with increase of population doubling level(PDL). S phase was decreased and G1 phase was increased with increase of PDL. Western blot analysis showed that levels of p16, p21 and p53 of senescent gingival fibroblasts(PDL41, PDL58) were higher than young fibroblasts(PDL27) and cdk4 were lower than young fibroblasts(PDL27). In conclusion, these results suggest that proliferative function of human gingival fibroblasts may be decreased by replicative senescence and its molecular mechanisms may be activatied with p16, p21, p53 and pRB, and repressed wtih cdk4.
Aging ; Blotting, Western ; Cell Aging* ; Cell Cycle Checkpoints ; Cell Cycle Proteins ; Cell Cycle* ; Cell Proliferation ; Cell Survival ; Fibroblasts* ; G1 Phase ; Gingiva ; Humans* ; S Phase

FAM60A,a cell cycle protein,is a subunit of the SIN3 transcription regulator family member A/histone deacetylase(SIN3-HDAC)complex and plays an important role in cell cycle regulation,cell morphology change,cell proliferation,differentiation and migration,early embryogenesis and so on.Studies in recent years have shown that FAM60A plays a role in the occurrence and development of tumors including human osteosarcoma,esophageal cancer,gastric cancer,lung cancer and liver cancer,providing a new research direction for tumor diagnosis and treatment.Based on the research results in recent years at home and abroad,this paper discussed the effects of FAM60A on cellular functions.
Cell Cycle Proteins ; Cell Differentiation ; Cell Proliferation ; DNA-Binding Proteins ; Humans ; Sin3 Histone Deacetylase and Corepressor Complex

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

染色质许可和DNA复制因子1（Cdt1）是复制起始许可的主要调控因子，也是组成复制前复合物的核心成员。细胞通过依赖Cdt1的波动水平，且在每个周期中通过调节其总量以确保DNA仅复制一次。Cdt1功能缺陷会造成DNA过度复制，最终导致基因组不稳定。虽然酵母中cdt1和人类Meier-Gorlin综合征（MGS）患者中的CDT1已被广泛研究，但缺乏脊椎动物模型。我们发现在硬骨鱼类分支的几个鲤形目物种（包括斑马鱼）中，Cdt1蛋白在其N末端插入一段其他脊椎动物中没有的独特无序序列。通过分析在cdt1基因中携带移码缺失的遗传性斑马鱼突变体（命名为cdt1^zju1 ），我们发现突变胚胎虽然几乎无任何早期胚胎表型异常，但成年突变斑马鱼却表现出侏儒症、生存能力降低的症状，以及性腺发育不全且不育。此外，我们同样发现除转录本cdt1-201外，斑马鱼还存在第二个cdt1转录本——cdt1-202，它是通过跳过外显子2产生，这在其他生物中暂无报道。有意思的是cdt1-202在cdt1-201纯合突变体中显著上调。上述研究结果表明，cdt1-202转录本可能可以补偿cdt1-201在早期发育过程中的功能损失，但不能补偿后期生长，这可支持斑马鱼作为研究人类MGS的遗传模型。
Animals ; Humans ; Zebrafish ; Growth Disorders ; Cell Cycle Proteins ; Gonads

Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor eff ects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory eff ect of S109 on CRM1 is reversible. Our data demonstrated that S109 signifi cantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the eff ects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.
Active Transport, Cell Nucleus ; Cell Cycle Checkpoints* ; Cell Cycle* ; Cell Proliferation* ; Cyclin D1 ; Kidney Neoplasms* ; Tumor Suppressor Proteins

The aim of present study was to investigate the effects of kaempferol on cellular proliferation and cell cycle arrest and explore the mechanism for these effects in human breast carcinoma MDA-MB-453 cells. Cells were treated with kaempferol at various concentrations (ranging from 1 to 200 microM) for 24 and 48 hrs. Kaempferol significantly inhibited cancer cell growth in cells exposed to 50 and 10 microM of kaempferol and incubated for 24 and 48 hrs, respectively. Exposure to kaempferol resulted in cell cycle arrest at the G2/M phase. Of the G2/M-phase related proteins, kaempferol down-regulated CDK1 and cyclin A and B in cells exposed to kaempferol. In addition, small DNA fragments at the sub-G0 phase were increased by up to 23.12 and 31.90% at 10 and 50 microM incubated for 24 and 48 hrs, respectively. The kaempferol-induced apoptosis was associated with the up-regulation of p53. In addition, the phosphorylation of p53 at the Ser-15 residue was observed with kaempferol. Kaempferol inhibits cell proliferation by disrupting the cell cycle, which is strongly associated with the induction of arrest at G2/M phase and may induce apoptosis via p53 phosphorylation in human breast carcinoma MDA-MB-453 cells.
Apoptosis ; Breast ; Breast Neoplasms ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Proliferation ; Cyclin A ; DNA ; Humans ; Kaempferols ; Phosphorylation ; Proteins ; Up-Regulation

BACKGROUND: Aberration of the cell cycle regulatory proteins has been reported to contribute to the development and progression of human malignancy. We studied the expression of G1/S cell cycle regulatory proteins to investigate the carcinogenesis in cutaneous squamous cell lesions. METHODS: We evaluated the expressions of p16, pRb, cyclin D1 and Ki-67 protein by immunonohistochemistry in cases of normal skin (n=15), seborrheic keratosis (SK; n=26), actinic keratosis (AK; n=30), Bowen's disease (BD; n=37), keratoacanthoma (KA; n=23), and squamous cell carcinoma (SCC; n=22). RESULTS: The Ki-67 expression gradually increased from SK, through AK, to BD. The expression of p16 was more increased in BD than that in AK. The decreased expressions of p16 and Rb, and the increased expression of cyclin D1 were observed to a greater degree in SCC than those in BD. The expressions of cyclin D1 and Ki-67 were higher in SCC than those in KA. CONCLUSIONS: The altered expressions of p16, Rb, and cyclin D1 were considered to be related to the carcinogenesis in the cutaneous squamous cell lesions. Therefore, immunohistochemical studies of the cell cycle regulatory proteins and a combined analysis may be helpful as an adjunct to the histomorphology in the diagnosis of cutaneous squamous cell lesions.
Bowen's Disease ; Carcinoma, Squamous Cell ; Cell Cycle ; Cell Cycle Proteins ; Cyclin D1 ; Humans ; Keratoacanthoma ; Keratosis, Actinic ; Keratosis, Seborrheic ; Skin

Retinoic acid plays an important role in the regulation of cell growth and differentiation. In our present study, we evaluated the effects of all-trans retinoic acid (RA) on cell proliferation and on the cell cycle regulation of human gingival fibroblasts (HGFs). Cell proliferation was assessed using the MTT assay. Cell cycle analysis was performed by flow cytometry, and cell cycle regulatory proteins were determined by western blot. Cell proliferation was increased in the presence of a 0.1 nM to 1 microM RA dose range, and maximal growth stimulation was observed in cells exposed to 1 nM of RA. Exposure of HGFs to 1 nM of RA resulted in an augmented cell cycle progression. To elucidate the molecular mechanisms underlying cell cycle regulation by RA, we measured the intracellular levels of major cell cycle regulatory proteins. The levels of cyclin E and cyclin-dependent kinase (CDK) 2 were found to be increased in HGFs following 1 nM of RA treatment. However, the levels of cyclin D, CDK 4, and CDK 6 were unchanged under these conditions. Also after exposure to 1 nM of RA, the protein levels of p21WAF1/CIP1 and p16INK4A were decreased in HGFs compared with the control group, but the levels of p53 and pRb were similar between treated and untreated cells. These results suggest that RA increases cell proliferation and cell cycle progression in HGFs via increased cellular levels of cyclin E and CDK 2, and decreased cellular levels of p21WAF1/CIP1 and p16INK4A.
Blotting, Western ; Cell Cycle ; Cell Cycle Proteins ; Cell Proliferation ; Cyclin D ; Cyclin E ; Cyclins ; Fibroblasts ; Flow Cytometry ; Humans ; Phosphotransferases ; Tretinoin