Expression of cyclin D1 and p21(WAF1/CIP1) in human gastric carcinoma and its clinicopathologic significance.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15114-e15114
Author(s):  
Vasiliki Michalaki ◽  
Theodosios Theodosopoulos ◽  
Agathi Kondi- Pafiti ◽  
Constantine G. Gennatas
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Gastric Carcinoma ◽  
Cyclin D1 ◽  
Gastric Epithelium ◽  
Nuclear Staining ◽  
Cell Cycle Regulators ◽  
Diffuse Type ◽  
Clinicopathological Findings ◽  
P21 Waf1

e15114 Background: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers. Alterations in cell cycle regulators and subsequent deregulation of the cell cycle are frequently involved in tumorigenesis and/or tumor progression. The aim of our study was to detect the abnormal expression of cyclin D1 and p21(WAF1/CIP1)in gastric carcinoma and investigate its clinicopathologic significance. Methods: Proteins of cyclin D1 were detected by immunohistochemistry in 80 cases of advanced gastric carcinoma, and 30 cases of benign gastric diseases (chronic gastritis, atrophic gastritis, gastric metaplasia, and gastric dysplasia). From each patient formaldehyde–fixed paraffin sections were stained and examined by immunohistochemistry using monoclonal antibodies.All tumor cells with distinct nuclear staining were considered positive. Results: Sixty-five patients were male and forty five female. Normal gastric epithelium showed consistently positive immunostain for p21WAF1/CIP1. Loss of p21WAF1/CIP1 expression was noted in 65% of intestinal type adenocarcinoma and in 90% of diffuse type adenocarcinoma. Overexpression of cyclin D1 was detected in 90% of advanced gastric carcinomas. Among the various clinicopathological findings, overexpression of cyclin D1 was associated with lymph-node metastasis (P=0.003) and recurrence (P=0.044). Loss of p21WAF1/CIP1 expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.001). Conclusions: These findings suggest that overexpression of cyclin D1 is a frequent finding in gastric cancer and immunohistochemical analysis for cell cycle regulators, might be a useful prognostic indicator in gastric cancer.

Expression of cell-cycle regulatory proteins cyclin D1, cyclin E, and their inhibitor p21 WAF1/CIP1 in gastric cancer

1999 ◽  
Vol 189 (2) ◽  
pp. 186-193 ◽  
Author(s):  
Wolfram M�ller ◽  
Tsuyoshi Noguchi ◽  
Hans-Christian Wirtz ◽  
Gerhard Hommel ◽  
Helmut E. Gabbert
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cyclin E ◽  
Regulatory Proteins ◽  
Cell Cycle Regulatory Proteins ◽  
P21 Waf1

Effect of Chrysanthemum flavonoids on growth and cell cycle regulators of gastric cancer cell

2010 ◽  
Vol 34 (8) ◽  
pp. S50-S50
Author(s):  
Xiaoyan Pan ◽  
Xinmei Zhou ◽  
Guangtao Xu ◽  
Lingfen Miao ◽  
Shuoru Zhu
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cell Cycle Regulators

Vitamin C affects G0/G1 cell cycle and autophagy by downregulating of cyclin D1 in gastric carcinoma cells

2021 ◽  
Vol 85 (3) ◽  
pp. 553-561
Author(s):  
Chenxia Ren ◽  
Cuiling Wu ◽  
Changqing Yang ◽  
Changhong Lian
Keyword(s):  
Cell Cycle ◽  
Gastric Carcinoma ◽  
Vitamin C ◽  
Cyclin D1 ◽  
Bioinformatics Analysis ◽  
Carcinoma Cells ◽  
Cell Cycle Pathway ◽  
Differential Gene ◽  
Regulation Of Cell Cycle ◽  
Amp Activated Protein Kinase

ABSTRACT Vitamin C has re-emerged as a promising anticancer agent. This study attempts to analyze the differential gene expression of profiles GSE11919 to look for some clues, and the most significant cell cycle pathway caused by vitamin C was identified by integrated bioinformatics analysis. Inspired by this, we investigated the effect of vitamin C treatment on gastric carcinoma cells by detection of cell cycle, apoptosis, and autophagy. Vitamin C significantly elevated the percentage of cells at G0/G1 phase, whereas the percentage of S phase cells was decreased. Meanwhile, vitamin C treatment resulted in downregulation of cell cycle-related protein Cyclin D1. We deduced that the downregulation of Cyclin D1 by vitamin C accompanied by significantly increased 5′AMP-activated protein kinase and induced autophagy in MKN45 cells. These results suggest that vitamin C has the antiproliferation effect on gastric carcinoma cells via the regulation of cell cycle and autophagy by Cyclin D1.

scholarly journals Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions

2003 ◽  
pp. 81-87 ◽  
Author(s):  
GE Thomopoulou ◽  
S Tseleni-Balafouta ◽  
AC Lazaris ◽  
H Koutselini ◽  
N Kavantzas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Control ◽  
Parathyroid Glands ◽  
Considerable Proportion ◽  
Parathyroid Cell ◽  
Apoptotic Cells ◽  
Cell Cycle Regulators ◽  
Suppressor Activity ◽  
Fhit Protein

OBJECTIVE: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT). DESIGN: TIssue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. METHODS: In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. RESULTS: Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P=0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas. CONCLUSIONS: In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.

Cyclin D: CDK4/6 Kinase Activity, Regulated by GATA-1, Is Required for Megakaryocyte Polyploidization.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 780-780
Author(s):  
Andrew G. Muntean ◽  
Liyan Pang ◽  
Mortimer Poncz ◽  
Steve Dowdy ◽  
Gerd Blobel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cyclin D1 ◽  
Kinase Activity ◽  
Fetal Liver ◽  
Cyclin D3 ◽  
Luciferase Reporter ◽  
Cell Cycle Regulators ◽  
Wild Type

Abstract Megakaryocytes, which fragment to give rise to platelets, undergo a unique form of cell cycle, termed endomitosis, to become polyploid and terminally differentiate. During this process, cells transverse the cell cycle but the late stages of mitosis are bypassed to lead to accumulation of DNA up to 128N. While the mechanisms of polyploidization in megakaryocytes are poorly understood, a few cell cycle regulators, such as cyclin D3, have been implicated in this process. Hematopoietic transcription factors, including GATA-1 and RUNX1 are also essential for polyploidization, as both GATA1-deficient and RUNX1-null megakaryocytes undergo fewer rounds of endomitosis. Interestingly, GATA-1 deficient megakaryocytes are also smaller than their wild-type counterparts. However, the link between transcription factors and the growth and polyploidization of megakaryocytes has not been established. In our studies to identify key downstream targets of GATA-1 in the megakaryocyte lineage, we discovered that the cell cycle regulators cyclin D1 and p16 were aberrantly expressed in the absence of GATA-1: cyclin D1 expression was reduced nearly 10-fold, while that of p16ink4a was increased 10-fold. Luciferase reporter assays revealed that GATA-1, but not the leukemic isoform GATA-1s, promotes cyclinD1 expression. Consistent with these observations, megakaryocytes that express GATA-1s in place of full-length GATA-1 are smaller than their wild-type counterparts. Chromatin immunoprecipitation studies revealed that GATA-1 is bound to the cyclin D1 promoter in vivo, in primary fetal liver derived megakaryocytes. In contrast, GATA-1 is not associated with the cyclin D1 promoter in erythroid cells, which do not become polyploid. Thus, cyclin D1 is a bona fide GATA-1 target gene in megakaryocytes. To investigate whether restoration of cyclin D1 expression could rescue the polyploidization defect in GATA-1 deficient cells, we infected fetal liver progenitors isolated from GATA-1 knock-down mice with retroviruses harboring the cyclin D1 cDNA (and GFP via an IRES element) or GFP alone. Surprisingly, expression of cyclin D1 did not increase the extent of polyploidization of the GATA-1 deficient megakaryocytes. However, co-overexpression of cyclin D1 and Cdk4 resulted in a dramatic increase in polyploidization. Consistent with the model that cyclinD:Cdk4/6 also regulates cellular metabolism, we observed that the size of the doubly infected cells was also significantly increased. Finally, in support of our model that cyclin D:Cdk4/6 kinase activity is essential for endomitosis, we discovered that introduction of wild-type p16 TAT fusion protein, but not a mutant that fails to interact with Cdk4/6, significantly blocked polyploidization of primary fetal liver derived megakaryocytes. Taken together, our data reveal that the process of endomitosis and cell growth relies heavily on cyclinD:Cdk4/6 kinase activity and that the maturation defects in GATA-1 deficient megakaryocytes are due, in part, to reduced Cyclin D1 and increase p16 expression.

scholarly journals Epithelial-mesenchymal transition in main types of gastric carcinoma

2021 ◽  
Vol 10 (2) ◽  
pp. 13-20
Author(s):  
I.V. Vasilenko ◽  
◽  
R.B. Kondratyk ◽  
I.S. Grekov ◽  
A.M. Yarkov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Mixed Type ◽  
Epithelial Mesenchymal Transition ◽  
Rapid Development ◽  
Tumor Formation ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Vimentin Expression ◽  
Mesenchymal Transition

Introduction. The rapid development of basic science enabled us to significantly expand our understanding of various intercellular interactions. Epithelial-mesenchymal transition (EMT) is known to play a key role in certain tissue formation in the embryonic period. However, recent data show that EMT can also be observed in some pathological conditions, in particular, in various neoplasm development. This suggests that there are a number of alternative and fundamentally new mechanisms for the tumor formation and progression. Thus, EMT, which occurs in carcinomas, increases the invasiveness, immunoresistance, immunity to therapy, and the metastatic potential. Knowledge of EMT features and their timely recognition in morphological tumor diagnosis is of great predictive importance for patients. The aim of the research was to study the morphologi-cal features of epithelial-mesenchymal transition in the main types of gastric cancer. Materials and methods. We studied specimens of gastric carcinomas (N=64) including 31 cases of diffuse type, 19 cases of intestinal type, and 14 cases of mixed type. Results. All cases of the diffuse carcinoma group showed spread EMT features, which appeared already in the mucosa and completed with positive vimentin expression in 93.5% of cases. The malignant cell prolifera-tive activity was low; however, in 29% of cases we detected areas of moderate or even high activity. In the intestinal type gastric cancer, EMT developed as a result of tumor progression, it arose more often in the deeper layers and was incomplete and focal. As a rule, the proliferative activity of tumor cells was high and moderate. Vascular invasion occurred more often in diffuse type (90.3%), less often in mixed type (71.4%), and even less often in the intestine type (55.8%) gastric carcinoma. Conclusion. The variety of morphological features of EMT, its frequency, prevalence, completeness, and sequence in the development of various types of gastric cancer determines the features of their clinical manifestation and influences their further management. Keywords: gastric cancer, diagnosis, histological main types, EMT, morphopathology

scholarly journals P-013 Prognostic significance of cyclin D1 and p21 (WAF1/CIP1) in Gastric Cancer

2016 ◽  
Vol 27 ◽  
pp. ii4
Author(s):  
V. Michalaki ◽  
T. Theodosopoulos ◽  
N. Dafnios ◽  
A. Vezakis ◽  
E. Karvouni ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cyclin D1 ◽  
Prognostic Significance ◽  
P21 Waf1

Clinical implication of cell-cycle regulators on advanced gastric carcinoma

2001 ◽  
Vol 120 (5) ◽  
pp. A162-A162
Author(s):  
M LEE ◽  
S MYUNG ◽  
H JUNG ◽  
G KANG ◽  
S YANG ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gastric Carcinoma ◽  
Clinical Implication ◽  
Cell Cycle Regulators ◽  
Advanced Gastric Carcinoma

The cell cycle regulation of anti-cancer bioactive peptide (ACBP) on gastric cancer cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15087-15087
Author(s):  
X. Su ◽  
X. Ouyang ◽  
G. Xu ◽  
J. Shen ◽  
M. Yan
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Gastric Cancer ◽  
Human Gastric Cancer Cell ◽  
Gastric Cancer Cell Lines

15087 Background: Anti-cancer bioactive peptide (ACBP) was extracted from the spleen of the goat suffered immune inducement by immunoreaction, supercentrifuge and ultra-filtration. Our previous studies have identified ACBP had significantly inhibited the growth of the human gastric cancer cell lines BGC-823 and MGC-803, the human rhinopharyngocele cell line CNE and the leukemic cell line. The in vivo experiments showed ACBP could dramatically repress the growth of tumor, and had few side-effects in the long-term toxic experiments. In clinical trials, ACBP could enhance the survival and life quality of the patients with advanced gastric cancer. In this study, we will explore the influence and mechanism of the effect of ACBP on cell cycle using human gastric cancer cell lines BGC-823 and MGC-803. Methods: Human gastric cancer cell lines BGC-823 and MGC-803 were cultured with different concentrations (10–25 ug/ml) of ACBP. The MTT method was employed to measure the growth inhibition rates of the cells with different concentrations of ACBP; the morphological changes were observed under the light microscope; the semi-quantitative RT-PCR was used to assay the changes of mRNA for p16,p21,p27,c-myc,cyclin D1,bax,bcl-2 gene. Results: Different concentrations of ACBP in the range of 10.0–25.0 μg/ml could inhibit the growth of BGC-823 and MGC-803 cell and such effect was both concentration and time dependent. 25.0 μg/ml ACBP had an inhibition rate (IR) of 84.4%, 72.3% and a median concentration (IC50) of 17.86 μg/ml, 13.16 ug/ml. After ACBP treatment, the cells showed typical apoptotic changes under the light microscope. On RT-PCR, the expressions of p16,p21,p27,bax mRNA in the two cell lines were markedly increased after ACBP treatment. On the contrary, the expression of c-myc,cyclin D1,bcl-2 mRNA in the two cell lines were obviously decreased after ACBP treatment. Conclusion: ACBP had markedly repressed the growth of BGC-823 and MGC-803 cell lines through inducing the cellular apoptosis. The possible mechanism is ACBP affects the cell cycle molecules expression including p16,p21,p27,cyclin D1 and regulate c-myc,bcl-2 and bax to induce apoptosis. No significant financial relationships to disclose.

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