The Role of Cell Cycle Regulatory Protein, Cyclin D1, in the Progression of Thyroid Cancer

Purpose Biliary tract adenocarcinomas (BTAs), although anatomically related, arise through ill-defined and possibly different location-related pathogenetic pathways. This clinicopathologic study characterizes differences in cell cycle–regulatory protein expression across the spectrum of BTA. Methods Tissue microarrays were prepared from paraffin-embedded surgical specimens with triplicate cores of BTA and benign tissue. Immunohistochemical expression of p53, cyclin D1, p21, Bcl2, p27, Mdm2, and Ki-67 was assessed, and the results were correlated with pathologic variables and survival. Hierarchical clustering was used to partition the data based on protein expression, and then the data were analyzed according to anatomic location. Results Tissue from 128 surgical patients (1992 to 2002) was obtained. Tumor sites of origin were intrahepatic cholangiocarcinoma (IH; n = 23), hilar cholangiocarcinoma (Hilar; n = 54), gallbladder (GB; n = 32), and distal bile duct (Distal; n = 19). p27 expression decreased progressively from proximal to distal in the biliary tree and correlated with location-related differences in outcome; cyclin D1 and Bcl2 overexpression also varied according to anatomic site. Aberrant p53 staining and cyclin D1 overexpression were lower in papillary tumors compared with the more common sclerosing tumors. The expression profiles of GB and Hilar were more similar to each other than either was to IH or Distal (86% clustering in the first partition). After an R0 resection, overexpression of Mdm2 (P = .0062) and absent p27 expression (P = .0165) independently predicted poor outcome. Conclusion BTAs differentially express cell cycle–regulatory proteins based on tumor location and morphology. Prognostic roles were identified for Mdm2 and p27. Overlap in the pathogenesis of GB and Hilar tumors was suggested.

Download Full-text

Cell cycle regulatory protein expression in multinucleated giant cells: Do they proliferate?

10.26226/morressier.596dfd5bd462b80292387f76 ◽

2017 ◽

Author(s):

Tibor Krenacs

Keyword(s):

Cell Cycle ◽

Protein Expression ◽

Regulatory Protein ◽

Giant Cells ◽

Multinucleated Giant Cells ◽

Cell Cycle Regulatory Protein

Download Full-text

Distinctive cell cycle regulatory protein profiles by adenovirus delivery of p53 in human papillomavirus-associated cancer cells

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2006.00393.x ◽

2006 ◽

Vol 16 (2) ◽

pp. 698-707 ◽

Cited By ~ 2

Author(s):

H.-S. JIN ◽

S.-M. BAE ◽

Y.-W. KIM ◽

J.-M. LEE ◽

S.-E. NAMKOONG ◽

...

Keyword(s):

Cell Cycle ◽

Human Papillomavirus ◽

Cancer Cells ◽

Regulatory Protein ◽

Protein Profiles ◽

Cell Cycle Regulatory Protein ◽

Distinctive Cell

Download Full-text

Hypoxia Alters Cell Cycle Regulatory Protein Expression and Induces Premature Maturation of Oligodendrocyte Precursor Cells

PLoS ONE ◽

10.1371/journal.pone.0004739 ◽

2009 ◽

Vol 4 (3) ◽

pp. e4739 ◽

Cited By ~ 20

Author(s):

Ravi Shankar Akundi ◽

Scott A. Rivkees

Keyword(s):

Cell Cycle ◽

Protein Expression ◽

Regulatory Protein ◽

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Cell Cycle Regulatory Protein ◽

Oligodendrocyte Precursor

Download Full-text

Differential Expression of Cyclin D1 in Breast Papillary Carcinomas and Benign Papillomas

Archives of Pathology & Laboratory Medicine ◽

10.5858/1999-123-0152-deocdi ◽

1999 ◽

Vol 123 (2) ◽

pp. 152-156

Author(s):

M. Saddik ◽

R. Lai ◽

L. J. Medeiros ◽

A. McCourty ◽

R. K. Brynes

Keyword(s):

Cyclin D1 ◽

Papillary Carcinoma ◽

Regulatory Protein ◽

Immunohistochemical Method ◽

Breast Carcinomas ◽

Ki 67 ◽

Cell Cycle Regulatory Protein ◽

The Difference ◽

Breast Tissues ◽

Formalin Fixed

Abstract Objectives.—Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult using histologic criteria. Since cyclin D1, a G1 cell-cycle regulatory protein, is detectable immunohistochemically in a subset of breast carcinomas but not in benign breast tissues, we hypothesized that cyclin D1 immunoreactivity may be a marker for identifying papillary carcinoma. Methods.—Using an immunohistochemical method, we assessed for cyclin D1 expression in 8 breast papillomas and 6 papillary carcinomas, all of which were formalin fixed, routinely processed, and paraffin embedded. Cyclin D1 positivity also was compared with the overall proliferation rate, which was assessed by using the proliferation marker Ki-67. In each case, a 200-cell count was performed to obtain the percentage of cells positive for these 2 markers. Results.—The percentage of cyclin D1–positive cells was significantly higher in papillary carcinomas (89% ± 18%; range, 53%–98%) than in papillomas (8% ± 7%; range, 0%–19%). This difference was highly statistically significant (P < .0001). Although the difference in Ki-67 positivity between these 2 groups was also statistically significant (P = .01), separation of papillary carcinomas and papillomas by Ki-67 immunoreactivity was less clear because of overlapping values between groups: 13% ± 6%; range, 9% to 23% for papillary carcinomas versus 8% ± 2%; range, 6% to 12% for papillomas. Conclusions.—These results support the notion that cyclin D1 is a useful marker for distinguishing breast papillomas from papillary carcinomas. The marker Ki-67 is also helpful, but is less useful than cyclin D1, owing to the overlap in Ki-67 results in papillomas and papillary carcinomas.

Download Full-text

Expression of Cell Cycle Proteins P21 waf1/Cip1 , P27 kip1 , Cyclin D1 and CDK4 in Blood Vessels of Angiotensin II-Infused Rats. Role of AT 1 Receptors.

Hypertension ◽

10.1161/hyp.36.suppl_1.707-b ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 707-707

Author(s):

Quy N Diep ◽

Mohammed El Mabrouk ◽

Rhian M Touyz ◽

Ernesto L Schiffrin

Keyword(s):

Cell Cycle ◽

Angiotensin Ii ◽

Dna Synthesis ◽

Cyclin D1 ◽

Blood Vessels ◽

Thymidine Incorporation ◽

Mesenteric Arteries ◽

Ang Ii

P79 Angiotensin II (Ang II) is an important modulator of cell growth via AT 1 receptors, as demonstrated both in vivo and in vitro . Here, we investigated the role of different proteins involved in the cell cycle, including cyclin D1, cyclin-dependent kinase 4 (cdk4) and cdk inhibitors p21 and p27 in blood vessels of Ang II-infused rats and the effect therein of the AT 1 receptor antagonist losartan. Male Sprague Dawley rats were infused for 7 days with Ang II (120 ng/kg/min s.c.) and/or treated with losartan (10 mg/kg/day orally). DNA synthesis in mesenteric arteries was evaluated by radiolabeled 3 H-thymidine incorporation. The expression of p21, p27, cyclin D1, cdk4 and E2F, which play critical roles during G1-phase of the cell cycle process, was examined by Western blot analysis. Tail cuff systolic blood pressure (mmHg) was elevated (p<0.05, n=9) in Ang II-infused rats (161.3±8.2) vs. controls (110.1±5.3) and normalized by losartan (104.4±3.2). Radiolabeled 3 H-thymidine incorporation (cpm/100 μg DNA) showed that Ang II-infusion significantly increased DNA synthesis (152±5 vs. 102±6, p<0.05). Expression of p21 and p27 was significantly decreased in the Ang II group to 23.2±10.4% and 10.3±5.3% of controls, respectively, whereas expression of cyclin D1 and cdk4 was significantly increased in the Ang II group to 213.7±8% and 263.6±37% of controls, respectively. These effects induced by Ang II infusion was normalized in the presence of losartan. Ang II had no effect on the expression of E2F. Thus, when AT 1 receptors are stimulated in vivo , DNA synthesis is enhanced in blood vessels by activation of cyclin D1 and cdk4. Reduction in cell cycle kinase inhibitors p21 and p27 may contribute to activation of growth induced by in vivo AT 1 receptor stimulation.

Download Full-text

The Cell-Cycle Regulatory Protein p21CIP1/WAF1 Is Required for Cytolethal Distending Toxin (Cdt)-Induced Apoptosis

Pathogens ◽

10.3390/pathogens9010038 ◽

2020 ◽

Vol 9 (1) ◽

pp. 38 ◽

Cited By ~ 2

Author(s):

Bruce J. Shenker ◽

Lisa M. Walker ◽

Ali Zekavat ◽

Robert H. Weiss ◽

Kathleen Boesze-Battaglia

Keyword(s):

Cell Cycle ◽

Human Lymphocytes ◽

Regulatory Protein ◽

Cytolethal Distending Toxin ◽

The Novel ◽

Cell Cycle Regulatory Protein ◽

Cycle Arrest ◽

Induced Apoptosis ◽

Hsp 90 ◽

Lymphoid Cell Lines

The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) induces lymphocytes to undergo cell-cycle arrest and apoptosis; toxicity is dependent upon the active Cdt subunit, CdtB. We now demonstrate that p21CIP1/WAF1 is critical to Cdt-induced apoptosis. Cdt induces increases in the levels of p21CIP1/WAF1 in lymphoid cell lines, Jurkat and MyLa, and in primary human lymphocytes. These increases were dependent upon CdtB’s ability to function as a phosphatidylinositol (PI) 3,4,5-triphosphate (PIP3) phosphatase. It is noteworthy that Cdt-induced increases in the levels of p21CIP1/WAF1 were accompanied by a significant decline in the levels of phosphorylated p21CIP1/WAF1. The significance of Cdt-induced p21CIP1/WAF1 increase was assessed by preventing these changes with a two-pronged approach; pre-incubation with the novel p21CIP1/WAF1 inhibitor, UC2288, and development of a p21CIP1/WAF1-deficient cell line (Jurkatp21−) using clustered regularly interspaced short palindromic repeats (CRISPR)/cas9 gene editing. UC2288 blocked toxin-induced increases in p21CIP1/WAF1, and JurkatWT cells treated with this inhibitor exhibited reduced susceptibility to Cdt-induced apoptosis. Likewise, Jurkatp21− cells failed to undergo toxin-induced apoptosis. The linkage between Cdt, p21CIP1/WAF1, and apoptosis was further established by demonstrating that Cdt-induced increases in levels of the pro-apoptotic proteins Bid, Bax, and Bak were dependent upon p21CIP1/WAF1 as these changes were not observed in Jurkatp21− cells. Finally, we determined that the p21CIP1/WAF1 increases were dependent upon toxin-induced increases in the level and activity of the chaperone heat shock protein (HSP) 90. We propose that p21CIP1/WAF1 plays a key pro-apoptotic role in mediating Cdt-induced toxicity.

Download Full-text