A New Perspective on Cyclin D1: Beyond Cell Cycle Regulation

2013 ◽  
pp. 289-304
Author(s):  
Chenguang Wang ◽  
Timothy G. Pestell ◽  
Richard G. Pestell
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Regulation ◽  
New Perspective ◽  
Cycle Regulation

scholarly journals Elucidation of β-Catenin Cyclin D1 Pathway in Oral Squamous Cell Carcinoma

2018 ◽  
Vol 2 (2) ◽  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Squamous Cell ◽  
Cell Cycle Regulation ◽  
Mrna Level ◽  
Wnt Signaling Pathway ◽  
Cycle Regulation

Background: Oral cancer is sixth most common cancer in India with poor overall disease free survival. In last decade major changes in the cancer management has happened but no such advantage has been seen in the survival of oral cancer patients. One major reason for the poor survival of head and neck squamous cell carcinoma (HNSCC) is lack of good predictive and prognostic biomarkers. Different studies have shown that in cancer cells, cell-cycle regulatory protein expression is altered. Cyclin D1 is a key regulatory molecule in cell cycle regulation. Many of the molecular alterations that cause abnormal biologic behaviour of cancer cells are based on aberrations of cell cycle regulation. Studies have demonstrated that Cyclin D1, c-Myc and MMP7 were important target genes of WNT signaling pathway and overexpression of them was highly associated with accumulation of β-Catenin and mutational defects of the WNT signaling pathway in numerous tumor types. Aim: This study was planned to characterize the β-Catenin and Cyclin D1 transcript level expression pattern in oral squamous cell carcinoma (OSCC) samples. Materials and Methods: Expression patterns of β-Catenin and Cyclin D1 were studied in OSCC at the transcript and protein levels by using qRT-PCR and immunohistochemistry (IHC) respectively. χ2, t-tests and ANOVA were used for the statistical analyses. Results: β-Catenin and Cyclin D1 were significantly overexpressed in oral squamous cell carcinoma cases when compared to normal. Correlation regression analysis showed the expression of Cyclin D1 and β-Catenin at mRNA level were positively correlated. Further, in immunohistochemical analysis β-Catenin showed cytoplasmic staining rather than nuclear. Conclusion: It is concluded that β-Catenin and Cyclin D1 mRNA level analysis using Real-time PCR could serve as biomarkers in oral squamous cell carcinoma since their expression is consistently altered in majority of the oral squamous cell carcinoma samples.

Association of cyclin D2 downregulation with adverse prognostic factors and survival: Analysis of D-type cyclins, cyclin E1, p27, and ki-67 mRNA in breast carcinomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22208-e22208
Author(s):  
Helena Brizova ◽  
Marcela Mrhalova ◽  
Roman Kodet
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Regulation ◽  
Mrna Level ◽  
Breast Carcinomas ◽  
Time To Event ◽  
Cyclin D2 ◽  
Ki 67 ◽  
Quantitative Level ◽  
Cycle Regulation

e22208 Background: In a normal mammary gland D-type and E1 cyclins play a significant role in the cell cycle control. Not surprisingly, they are considered to have an oncogenic potential and belong among the most commonly overexpressed genes in breast cancer. Besides, cyclin D2 overexpression is associated with an inhibition of cyclin D1 phosphorylation and with an increase of the p27 inhibitor. Such a complex cell cycle regulation is realized at the quantitative level and results in the proliferation activity control. Therefore, we analyzed the molecules involved in the cell cycle regulation together with the proliferation marker Ki-67 at the quantitative level. Methods: We examined cyclin D1, D2, D3, E1, and p27 and Ki-67 mRNA level by qRT-PCR in 95 fresh frozen invasive ductal breast carcinomas and in 15 non-neoplastic breast tissues. In patients with the carcinoma we correlated the mRNA levels with the ERBB-2 positivity, estrogen and progesterone receptor status, proliferation rate, cyclin D1 protein expression, CCDN1 gene amplification, grade, lymph node status, tumor size and age at diagnosis. We looked for a correlation with overall survival and time to event in 70 patients with available long term follow-up data. Results: The only significant association found in this analysis related to cyclin D2. In comparison with non-neoplastic controls we observed cyclin D2 mRNA down-regulation in breast carcinomas and it was inversely correlated with a higher tumor grade and its greater size, which are considered as parameters related to a less favorable prognosis. Moreover, cyclin D2 mRNA down-regulation together with cyclin D1 and D3 up-regulation revealed a significant association with decreased overall survival and time to event in multivariate analysis. Conclusions: The data indicate that down-regulated cyclin D2 mRNA correlates with a greater malignant potential of breast carcinoma. Thus, establishing cyclin D2 mRNA level may be used as a prognostically relevant investigation and along with other prognostically related data it has a potential in helping to identify patients with an adverse prognosis. Support CZ.2.16/3.1.00/24022 and 00064203.

scholarly journals Purification, Characterization, and Kinetic Mechanism of Cyclin D1·CDK4, a Major Target for Cell Cycle Regulation

1998 ◽  
Vol 273 (41) ◽  
pp. 26506-26515 ◽  
Author(s):  
Alexandros K. Konstantinidis ◽  
R. Radhakrishnan ◽  
Fei Gu ◽  
R. Nagaraja Rao ◽  
Wu-Kuang Yeh
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Regulation ◽  
Kinetic Mechanism ◽  
Cycle Regulation ◽  
Major Target

Abstract 3319: Cell cycle regulation of glioblastoma progression by cord blood stem cells is mediated by downregulation of cyclin D1

2011 ◽  
Author(s):  
Kiran Kumar Velpula ◽  
Venkata Ramesh Dasari ◽  
Andrew J. Tsung ◽  
Christopher S. Gondi ◽  
Jeffrey D. Klopfenstein ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cord Blood ◽  
Cyclin D1 ◽  
Cell Cycle Regulation ◽  
Blood Stem Cells ◽  
Cord Blood Stem Cells ◽  
Cycle Regulation

scholarly journals Inhibition of TFII-I-Dependent Cell Cycle Regulation by p53

2005 ◽  
Vol 25 (24) ◽  
pp. 10940-10952 ◽  
Author(s):  
Zana P. Desgranges ◽  
Jinwoo Ahn ◽  
Maria B. Lazebnik ◽  
Todd Ashworth ◽  
Caleb Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Cell Cycle Regulation ◽  
Cellular Proliferation ◽  
Cell Cycle Control ◽  
Genotoxic Stress ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Cycle Regulation

ABSTRACT The multifunctional transcription factor TFII-I is tyrosine phosphorylated in response to extracellular growth signals and transcriptionally activates growth-promoting genes. However, whether activation of TFII-I also directly affects the cell cycle profile is unknown. Here we show that under normal growth conditions, TFII-I is recruited to the cyclin D1 promoter and transcriptionally activates this gene. Most strikingly, upon cell cycle arrest resulting from genotoxic stress and p53 activation, TFII-I is ubiquitinated and targeted for proteasomal degradation in a p53- and ATM (ataxia telangiectasia mutated)-dependent manner. Consistent with a direct role of TFII-I in cell cycle regulation and cellular proliferation, stable and ectopic expression of wild-type TFII-I increases cyclin D1 levels, resulting in accelerated entry to and exit from S phase, and overcomes p53-mediated cell cycle arrest, despite radiation. We further show that the transcriptional regulation of cyclin D1 and cell cycle control by TFII-I are dependent on its tyrosine phosphorylation at positions 248 and 611, sites required for its growth signal-mediated transcriptional activity. Taken together, our data define TFII-I as a growth signal-dependent transcriptional activator that is critical for cell cycle control and proliferation and further reveal that genotoxic stress-induced degradation of TFII-I results in cell cycle arrest.

scholarly journals Regulation of the Cell Cycle by Focal Adhesion Kinase

1998 ◽  
Vol 143 (7) ◽  
pp. 1997-2008 ◽  
Author(s):  
Ji-He Zhao ◽  
Heinz Reiske ◽  
Jun-Lin Guan
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Dominant Negative ◽  
Brdu Incorporation ◽  
Dominant Negative Mutant ◽  
Wild Type ◽  
Erk Activation ◽  
Cycle Regulation

In this report, we have analyzed the potential role and mechanisms of integrin signaling through FAK in cell cycle regulation by using tetracycline-regulated expression of exogenous FAK and mutants. We have found that overexpression of wild-type FAK accelerated G1 to S phase transition. Conversely, overexpression of a dominant-negative FAK mutant ΔC14 inhibited cell cycle progression at G1 phase and this inhibition required the Y397 in ΔC14. Biochemical analyses indicated that FAK mutant ΔC14 was mislocalized and functioned as a dominant-negative mutant by competing with endogenous FAK in focal contacts for binding signaling molecules such as Src and Fyn, resulting in a decreases of Erk activation in cell adhesion. Consistent with this, we also observed inhibition of BrdU incorporation and Erk activation by FAK Y397F mutant and FRNK, but not FRNKΔC14, in transient transfection assays using primary human foreskin fibroblasts. Finally, we also found that ΔC14 blocked cyclin D1 upregulation and induced p21 expression, while wild-type FAK increased cyclin D1 expression and decreased p21 expression. Taken together, these results have identified FAK and its associated signaling pathways as a mediator of the cell cycle regulation by integrins.

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