scholarly journals Differences in Protein Expression and Gene Amplification of Cyclins between Colon and Rectal Adenocarcinomas

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Rolf Aamodt ◽  
Kristin Jonsdottir ◽  
Solveig Norheim Andersen ◽  
Johan Bondi ◽  
Geir Bukholm ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Gene Amplification ◽  
Cyclin E ◽  
Cyclin B1 ◽  
University Hospital ◽  
Cyclin D3 ◽  
Colon Cancers ◽  
Rectal Cancers ◽  
Cyclin A2

Adenocarcinomas of rectum and colon may be different with regard to the cellular biological basis for cancer development. A material of 246 rectal cancers removed surgically at Akershus University Hospital in the years 1992–2000 was investigated and was compared to a material of 219 colon cancers operated on at Akershus University Hospital during the years 1988, 1990 and 1997–2000. There were highly significant differences between the rectal and the colon cancers in the protein expression of cyclin D1, cyclin D3, cyclin E, nuclearβ-catenin, and c-Myc and in gene amplification of cyclin A2, cyclin B1, cyclin D1, and cyclin E. Gene amplification and protein expression in the rectal cancers correlated significantly for the cyclins B1, D3, and E. A statistically significant relation was observed between overexpression of cyclin A2 and local relapse of rectal carcinomas, as higher expression of cyclin A2 was associated with lower local recurrence rate.

scholarly journals Betel Nut Arecoline Induces Different Phases of Growth Arrest between Normal and Cancerous Prostate Cells through the Reactive Oxygen Species Pathway

2020 ◽  
Vol 21 (23) ◽  
pp. 9219
Author(s):  
Li-Jane Shih ◽  
Jia-Yu Wang ◽  
Jing-Yao Jheng ◽  
An-Ci Siao ◽  
Yen-Yue Lin ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cyclin D1 ◽  
Reactive Oxygen ◽  
Cyclin B1 ◽  
Cyclin D3 ◽  
Oxygen Species ◽  
Betel Nut ◽  
Prostate Cells

Prostate cancer (PCa) is a reproductive system cancer in elderly men. We investigated the effects of betel nut arecoline on the growth of normal and cancerous prostate cells. Normal RWPE-1 prostate epithelial cells, androgen-independent PC-3 PCa cells, and androgen-dependent LNCaP PCa cells were used. Arecoline inhibited their growth in dose- and time-dependent manners. Arecoline caused RWPE-1 and PC-3 cell cycle arrest in the G2/M phase and LNCaP cell arrest in the G0/G1 phase. In RWPE-1 cells, arecoline increased the expression of cyclin-dependent kinase (CDK)-1, p21, and cyclins B1 and D3, decreased the expression of CDK2, and had no effects on CDK4 and cyclin D1 expression. In PC-3 cells, arecoline decreased CDK1, CDK2, CDK4, p21, p27, and cyclin D1 and D3 protein expression and increased cyclin B1 protein expression. In LNCaP cells, arecoline decreased CDK2, CDK4, and cyclin D1 expression; increased p21, p27, and cyclin D3 expression; had no effects on CDK1 and cyclin B1 expression. The antioxidant N-acetylcysteine blocked the arecoline-induced increase in reactive oxygen species production, decreased cell viability, altered the cell cycle, and changed the cell cycle regulatory protein levels. Thus, arecoline oxidant exerts differential effects on the cell cycle through modulations of regulatory proteins.

Anomalous High p27/KIP1 Expression in a Subset of Aggressive B-Cell Lymphomas Is Associated With Cyclin D3 Overexpression. p27/KIP1—Cyclin D3 Colocalization in Tumor Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 765-772 ◽  
Author(s):  
Margarita Sánchez-Beato ◽  
Francisca I. Camacho ◽  
Juan C. Martı́nez-Montero ◽  
Ana I. Sáez ◽  
Raquel Villuendas ◽  
...  
Keyword(s):  
B Cell ◽  
Cyclin D1 ◽  
Kinase Inhibitor ◽  
Cyclin E ◽  
Cyclin D3 ◽  
Nuclear Accumulation ◽  
Proliferation Index ◽  
B Cell Lymphomas ◽  
Proliferating Cells ◽  
P27 Kip1

Abstract p27 cyclin-dependent kinase inhibitor downregulation is essential for transition to the S phase of the cell cycle. Thus, proliferating cells in reactive lymphoid tissue show no detectable p27 expression. Nevertheless, anomalous high p27 expression has been shown to be present in a group of aggressive B-cell lymphomas with high proliferation index and adverse clinical outcome. This suggests that abnormally accumulated p27 protein has been rendered functionally inactive. We analyzed the causes of this anomalous presence of p27 in a group of aggressive B-cell lymphomas, including 54 cases of diffuse large B-cell lymphomas and 20 Burkitt’s lymphomas. We simultaneously studied them for p27, cyclin D3, cyclin D2, cyclin D1, and cyclin E expression, because it has been stated that high levels of expression of cyclin D1 or E lead to increased p27 levels in some cell types. A statistically significant association between p27 and cyclin D3 expression was found for the group as a whole. Additionally, when dividing the cases according to the level of expression of cyclin D3 by reactive germinal centers, it was observed that cases with stronger cyclin D3 expression also show higher p27 expression. The relationship between both proteins was also shown at a subcellular level by laser confocal studies, showing that in cases with high expression of both proteins there was a marked colocalization. Additional evidence in favor of p27 sequestration by cyclin D3 was provided by coimmunoprecipitation studies in a Burkitt’s cell line (Raji) showing the existence of cyclin D3/p27 complexes and the absence of CDK2/p27 complexes. These results could support the hypothesis that there are cyclin D3/p27 complexes in a subset of aggressive B-cell lymphomas in which p27 lacks the inhibitory activity found when it is bound to cyclin E/CDK2 complexes. This interaction between both proteins could lead to an abnormal nuclear accumulation, detectable by immunohistochemical techniques.

Anomalous High p27/KIP1 Expression in a Subset of Aggressive B-Cell Lymphomas Is Associated With Cyclin D3 Overexpression. p27/KIP1—Cyclin D3 Colocalization in Tumor Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 765-772 ◽  
Author(s):  
Margarita Sánchez-Beato ◽  
Francisca I. Camacho ◽  
Juan C. Martı́nez-Montero ◽  
Ana I. Sáez ◽  
Raquel Villuendas ◽  
...  
Keyword(s):  
B Cell ◽  
Cyclin D1 ◽  
Kinase Inhibitor ◽  
Cyclin E ◽  
Cyclin D3 ◽  
Nuclear Accumulation ◽  
Proliferation Index ◽  
B Cell Lymphomas ◽  
Proliferating Cells ◽  
P27 Kip1

p27 cyclin-dependent kinase inhibitor downregulation is essential for transition to the S phase of the cell cycle. Thus, proliferating cells in reactive lymphoid tissue show no detectable p27 expression. Nevertheless, anomalous high p27 expression has been shown to be present in a group of aggressive B-cell lymphomas with high proliferation index and adverse clinical outcome. This suggests that abnormally accumulated p27 protein has been rendered functionally inactive. We analyzed the causes of this anomalous presence of p27 in a group of aggressive B-cell lymphomas, including 54 cases of diffuse large B-cell lymphomas and 20 Burkitt’s lymphomas. We simultaneously studied them for p27, cyclin D3, cyclin D2, cyclin D1, and cyclin E expression, because it has been stated that high levels of expression of cyclin D1 or E lead to increased p27 levels in some cell types. A statistically significant association between p27 and cyclin D3 expression was found for the group as a whole. Additionally, when dividing the cases according to the level of expression of cyclin D3 by reactive germinal centers, it was observed that cases with stronger cyclin D3 expression also show higher p27 expression. The relationship between both proteins was also shown at a subcellular level by laser confocal studies, showing that in cases with high expression of both proteins there was a marked colocalization. Additional evidence in favor of p27 sequestration by cyclin D3 was provided by coimmunoprecipitation studies in a Burkitt’s cell line (Raji) showing the existence of cyclin D3/p27 complexes and the absence of CDK2/p27 complexes. These results could support the hypothesis that there are cyclin D3/p27 complexes in a subset of aggressive B-cell lymphomas in which p27 lacks the inhibitory activity found when it is bound to cyclin E/CDK2 complexes. This interaction between both proteins could lead to an abnormal nuclear accumulation, detectable by immunohistochemical techniques.

Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas

Blood ◽  
2008 ◽  
Vol 111 (12) ◽  
pp. 5683-5690 ◽  
Author(s):  
Iwona Wlodarska ◽  
Daan Dierickx ◽  
Vera Vanhentenrijk ◽  
Katrien Van Roosbroeck ◽  
Helena Pospís̆ilová ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Cyclin E ◽  
Central Nervous System Involvement ◽  
Cyclin D3 ◽  
Cyclin D ◽  
Cyclin D2 ◽  
Aberrant Expression ◽  
Mantle Cell ◽  
The Central Nervous System

Abstract The genetics of t(11;14)(q13;q32)/cyclin D1–negative mantle cell lymphoma (MCL) is poorly understood. We report here 8 MCL cases lacking t(11;14) or variant CCND1 rearrangement that showed expression of cyclin D1 (2 cases), D2 (2 cases), and D3 (3 cases). One case was cyclin D negative. Cytogenetics and fluorescence in situ hybridization detected t(2;12)(p11;p13)/IGK-CCND2 in one of the cyclin D2-positive cases and t(6;14)(p21;q32)/IGH-CCND3 in one of the cyclin D3-positive cases. Moreover, we identified a novel cryptic t(2;14)(p24;q32) targeting MYCN in 2 blastoid MCLs: one negative for cyclin D and one expressing cyclin D3. Interestingly, both cases showed expression of cyclin E. Notably, all 3 blastoid MCLs showed a monoallelic deletion of RB1 associated with a lack of expression of RB1 protein and monoallelic loss of p16. In sum-mary, this study confirms frequent aberrant expression of cyclin D2 and D3 in t(11;14)-negative MCLs and shows a t(11;14)-independent expression of cy-clin D1 in 25% of present cases. Novel findings include cyclin E expression in 2 t(11;14)-negative MCLs characterized by a cryptic t(2;14)(p24;q32) and identification of MYCN as a new lymphoma oncogene associated with a blastoid MCL. Clinically important is a predisposition of t(11;14)-negative MCLs to the central nervous system involvement.

scholarly journals Myogenic protein expression before and after resistance loading in 26- and 64-yr-old men and women

2004 ◽  
Vol 97 (4) ◽  
pp. 1329-1337 ◽  
Author(s):  
Marcas M. Bamman ◽  
Ronald C. Ragan ◽  
Jeong-su Kim ◽  
James M. Cross ◽  
Vernishia J. Hill ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Muscle Biopsy ◽  
Repeated Measures ◽  
Kinase Inhibitor ◽  
Mechanical Load ◽  
Cyclin B1 ◽  
Inhibitory Influence ◽  
Vastus Lateralis Muscle ◽  
Cyclin Dependent Kinase

Based on the growing body of evidence implicating an important role for myogenic regulatory factors (MRFs) in the adaptive responses of skeletal muscle to mechanical load, we tested the hypothesis that protein concentrations of MRFs as well as cell cycle proteins (i.e., cyclins and cyclin-dependent kinase inhibitors) would be altered after heavy leg resistance exercise (RE). Because we and others, however, have shown a blunted adaptive response to long-term resistance training in older (O) women [females (F)] compared with men (M), we also tested the hypothesis that these myogenic responses to RE would be influenced by age and gender. Twenty-two younger (Y) adults (20–35 yr, 11 YF, 11 YM) and 20 O adults (60–75 yr, 9 OF, 11 OM) consented to vastus lateralis muscle biopsy before and 24 h after a bout of RE using a regimen known to induce myofiber hypertrophy when performed 2–3 days/wk for several weeks (3 sets of 80% one-repetition maximum for squat, leg press, and knee extension). Protein concentrations of MRFs (MyoD, myogenin, myf-6), cyclin D1, cyclin B1, α-actin, and the cyclin-dependent kinase inhibitor p27kip were determined by immunoblotting. Data were analyzed by using age × gender × load repeated-measures ANOVA. Myogenin expression was 44% higher ( P < 0.05) in O compared with Y, and myf-6 tended to be higher in OF compared with YF (95%, P = 0.059). A significant gender × load interaction indicated that, in F, RE led to a reduction in p27kip (20%; P < 0.05), which was driven mainly by a 27% drop in OF. Levels of cyclin D1, cyclin B1, MyoD, myf-6, and α-actin were not influenced by age, gender, or loading. We report a novel finding in humans of markedly higher myogenin protein content in older sedentary muscle. The results do not, however, support the hypothesis that myogenic protein expression is altered 24 h after RE, irrespective of age or gender. Although the time point of postexercise muscle biopsy could be viewed as too early to capture maximal effects for most of these proteins, the significant decline in p27kip concentration found in OF suggests that mechanical load may provide one means of overcoming the inhibitory influence of p27kip.

scholarly journals Antitumor Effect of Pyrogallol via miR-134 Mediated S Phase Arrest and Inhibition of PI3K/AKT/Skp2/cMyc Signaling in Hepatocellular Carcinoma

2019 ◽  
Vol 20 (16) ◽  
pp. 3985 ◽  
Author(s):  
Hyojin Ahn ◽  
Eunji Im ◽  
Dae Young Lee ◽  
Hyo-Jung Lee ◽  
Ji Hoon Jung ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Expression ◽  
Cyclin E ◽  
S Phase ◽  
Carcinoma Cells ◽  
Antitumor Effects ◽  
Colon Cancers ◽  
Phase Arrest ◽  
Huh7 Cells ◽  
S Phase Arrest

Though Pyrogallol, one of the natural polyphenols, was known to have anti-inflammatory and antitumor effects in breast and colon cancers, the underlying antitumor mechanisms of Pyrogallol, still remain unclear so far. Here, the antitumor mechanisms of Pyrogallol were elucidated in Hep3B and Huh7 hepatocellular carcinoma cells (HCCs). Pyrogallol showed significant cytotoxicity and reduced the number of colonies in Hep3B and Huh7 cells. Interestingly, Pyrogallol induced S-phase arrest and attenuated the protein expression of CyclinD1, Cyclin E, Cyclin A, c-Myc, S-phase kinase-associated protein 2 (Skp2), p-AKT, PI3K, increased the protein expression of p27, and also reduced the fluorescent expression of Cyclin E in Hep3B and Huh7 cells. Furthermore, Pyrogallol disturbed the interaction between Skp2, p27, and c-Myc in Huh7 cells. Notably, Pyrogallol upregulated miRNA levels of miR-134, and conversely, miR-134 inhibition rescued the decreased expression levels of c-Myc, Cyclin E, and Cyclin D1 and increased the expression of p27 by Pyrogallol in Huh7 cells. Taken together, our findings provide insight that Pyrogallol exerts antitumor effects in HCCs via miR-134 activation-mediated S-phase arrest and inhibition of PI3K/AKT/Skp2/cMyc signaling as a potent anticancer candidate.

scholarly journals The Prognostic Value and Overexpression of Cyclin A Is Correlated with Gene Amplification of both Cyclin A and Cyclin E in Breast Cancer Patient

2006 ◽  
Vol 28 (3) ◽  
pp. 107-116 ◽  
Author(s):  
A. Husdal ◽  
G. Bukholm ◽  
I. R. K. Bukholm
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Gene Amplification ◽  
Cyclin E ◽  
Gene Mutations ◽  
Cyclin A ◽  
Tp53 Gene ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Tp53 Gene Mutations

Deregulation of cell cycle control is a hallmark of cancer. The primary cyclins (A, B1, D1, D3 and E) are crucial for cell cycle progression. Secondary cyclins (C and H) have putative indirect effects on cell cycle propulsion and are not previously evaluated in breast cancer. We have examined protein expression and gene amplification of cyclins in breast carcinomas and correlated the findings with clinical follow-up data. We have previously demonstrated that over-expression of cyclin A is associated with poor prognosis in breast cancer patients. In this study we wanted to evaluate the mechanisms behinde overexpression of cyclin A, as well as the impact of other cyclins, both at the gene level and at the protein level, on prognosis of breast cancer patients. The impact of TP53 gene mutations on gene amplification of cyclins was also evaluated. Methods: Real-Time Quantitative PCR was used to detect gene amplification of cyclins in tumour tissue from 86 patients operated for invasive breast carcinomas, while immunohistochemistry was applied to detect protein expression of the same cyclins. Result: Of the 80-breast tumour samples available for cyclin A gene amplification analyses, 26.7% (23/80) was defined to have cyclin A gene amplification. 37.2% (32/79) had cyclin B1 gene amplification, 82.6% (71/82) of the samples harboured amplification of cyclin C gene, 74.4% (64/82) had cyclin D1 gene amplification, 41.9% (36/86) had cyclin D3 gene amplification, 29.1% (25/81) of the patients had cyclin E gene amplification and 9.3% (8/86) of the samples showed amplification of the cyclin H gene. When correlation between gene amplification and protein expression was evaluated, we observed a statistical significant correlation between gene amplification and protein expression of cyclin A (p = 0.009) and cyclin D3 (p < 0.001). However, the correlation between gene amplification and protein expression of cyclin A, as well as the prognostic value of cyclin A overexpression, was affected by gene amplification of cyclin E. Gene amplification of none of the other cyclins was associated with patient prognosis. There was a statistical significant correlation between TP53 gene mutations and gene amplification of cyclins A, D3 and B1. No correlation was observed between gene amplification of secondary cyclins (H and C) and TP53 gene mutations. Conclusions: The overexpression of cyclin A is correlated to gene amplification of both cyclin A and cyclin E. Over-expression of cyclin A is associated with poor prognosis in breast cancer patients. When analysed in a multivariate analyses model, gene amplification as well as protein expression of none of the other cyclins than cyclin A are associated with patient prognosis in breast carcinomas. TP53 gene mutation seems to correlate with gene amplification of primary, but not secondary cyclins.

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