scholarly journals Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258878
Author(s):  
Jane C. Figueiredo ◽  
Michael N. Passarelli ◽  
Wei Wei ◽  
Dennis J. Ahnen ◽  
Jeffrey S. Morris ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Regulatory Protein ◽  
Colorectal Adenomas ◽  
P Value ◽  
Epithelial Proliferation ◽  
Ki 67 ◽  
Growth Ratio ◽  
Proliferation And Apoptosis ◽  
Serrated Lesions

Background Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. Methods We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. Results Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. Conclusions Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis. ClinicalTrials.gov Identifier: NCT00272324

Differential Cell Cycle–Regulatory Protein Expression in Biliary Tract Adenocarcinoma: Correlation With Anatomic Site, Pathologic Variables, and Clinical Outcome

2006 ◽  
Vol 24 (7) ◽  
pp. 1152-1160 ◽  
Author(s):  
William R. Jarnagin ◽  
David S. Klimstra ◽  
Michael Hezel ◽  
Mithat Gonen ◽  
Yuman Fong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Cyclin D1 ◽  
Biliary Tract ◽  
Expression Profiles ◽  
Regulatory Protein ◽  
R0 Resection ◽  
Anatomic Site ◽  
Ki 67 ◽  
Cell Cycle Regulatory Protein

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.

scholarly journals IMP3 Protein Overexpression Is Linked to Unfavorable Outcome in Laryngeal Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4306
Author(s):  
Diana Maržić ◽  
Blažen Marijić ◽  
Tamara Braut ◽  
Stefan Janik ◽  
Manuela Avirović ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Low Grade ◽  
Benign Lesions ◽  
Ki 67 ◽  
Neck Node

Background: The aim of this study was to (i) determine IMP3 protein expression in benign and malignant laryngeal lesions, (ii) compare its expression to Ki-67, p53, cyclin D1, and (iii) finally, to examine the prognostic power of IMP3 in squamous cell carcinomas of the larynx (LSSC). Methods: IMP3 protein expression was evaluated in 145 patients, including 62 LSCC, 45 dysplasia (25 with low and 20 with high-grade dysplasia), and 38 benign lesions (vocal cord polyps and nodules). Results: IMP3 was significantly higher expressed in LSCC compared to dysplasia and benign lesions (p < 0.001; p < 0.001, respectively). Similarly, higher expression patterns were observed for Ki-67 and p53, whereas cyclin D1 was equally distributed in all three lesions. IMP3 (p = 0.04) and Ki-67 (p = 0.02) expressions were significantly linked to neck node positivity, and IMP3 overexpression to worse disease-specific survival (p = 0.027). Conclusion: Since IMP3 showed significantly higher expression in laryngeal carcinomas, but not in high- or low-grade dysplasia, it serves as a useful marker to differentiate between invasive and noninvasive lesions. Higher IMP3 expression represented a significantly worse prognosticator for clinical outcomes of patients with squamous cell carcinoma of the larynx.

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

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 &lt; .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.

The role of immunohistochemistry in the diagnosis of cervical intraepithelial neoplasia of different severity

2016 ◽  
pp. 138-140
Author(s):  
S.I. Zhuk ◽  
◽  
O.A. Taran ◽  
A.N. Koshmienskaya ◽  
T.V. Lobastova ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cervical Intraepithelial Neoplasia ◽  
Precancerous Lesions ◽  
Molecular Genetic ◽  
Intraepithelial Neoplasia ◽  
Reproductive Age ◽  
Moderate Degree ◽  
Ki 67 ◽  
The Third ◽  
Diagnosis And Prognosis

The objective: the finding of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia of different severity to optimize the diagnosis and prognosis of the disease. Patients and methods. The study involved 42 women of reproductive age with cervical intraepithelial the neoplasia of the cervix varying degrees applied to the doctor of cervical pathology Zhitomir regional oncologic dispensary. All women (n=42) were divided into groups. The first group included 15 patients (35.7%) with cervical intraepithelial neoplasia with mild. The second group included 13 women (31%) with cervical intraepithelial neoplasia a moderate degree. The third group was represented by patients with cervical intraepithelial neoplasia with severe – 14 respondents (33.3 per cent). Results. Marker BCL-2 in patients of the first group was positive in 7 patients (46.7%), Smooth Muscule Actin was positive in 9 patients (60%) and Ki-67 was diagnosed in 8 of the surveyed women (53.3%). In the second group of BCL-2 was positive in 8 patients (61.5%), Clone 124, Smooth Muscule Actin, Clone 1A4 was positive in 9 patients (69.2%), and Ki-67 was diagnosed in 12 of the surveyed women (92.3%). Marker BCL-2 in patients of the third group was positive in 12 patients (85.7%), Smooth Muscule Actin was positive in 10 patients (71.4%) and Ki-67 was diagnosed in 13 of the surveyed women (92.9% ). Conclusion. Carcinogenesis is associated with molecular genetic damage to the cervix. Some of the products of this process can be used as prognostic and diagnostic markers of tumor progression. Determination of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia makes it possible to accurately verify the diagnosis and to predict the course of pathological changes in the flat epithelium of the cervix. Key words: cervical intraepithelial neoplasia, cervical cancer, morphological diagnostics of precancerous lesions, BCL-2, Smooth Muscule Actin, Ki-67.

2040-P: Chronic Activation of CREB by Islet Amyloid Increases Star (Steroidogenic Acute Regulatory Protein) Expression in Islets

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2040-P
Author(s):  
MEGHAN F. HOGAN ◽  
NATHALIE ESSER ◽  
ANDREW T. TEMPLIN ◽  
JOSEPH J. CASTILLO ◽  
SAKENEH ZRAIKA ◽  
...  
Keyword(s):  
Protein Expression ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Islet Amyloid ◽  
Chronic Activation ◽  
Steroidogenic Acute Regulatory

mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators

2005 ◽  
Vol 289 (6) ◽  
pp. C1457-C1465 ◽  
Author(s):  
Gustavo A. Nader ◽  
Thomas J. McLoughlin ◽  
Karyn A. Esser
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Cyclin D1 ◽  
Ribosomal Rna ◽  
Molecular Mechanisms ◽  
D1 Protein ◽  
Rna Content ◽  
Cyclin D1 Protein ◽  
Rb Phosphorylation ◽  
Myotube Hypertrophy

The purpose of this study was to identify the potential downstream functions associated with mammalian target of rapamycin (mTOR) signaling during myotube hypertrophy. Terminally differentiated myotubes were serum stimulated for 3, 6, 12, 24, and 48 h. This treatment resulted in significant myotube hypertrophy (protein/DNA) and increased RNA content (RNA/DNA) with no changes in DNA content or indices of cell proliferation. During myotube hypertrophy, the increase in RNA content was accompanied by an increase in tumor suppressor protein retinoblastoma (Rb) phosphorylation and a corresponding increase in the availability of the ribosomal DNA transcription factor upstream binding factor (UBF). Serum stimulation also induced an increase in cyclin D1 protein expression in the differentiated myotubes with a concomitant increase in cyclin D1-dependent cyclin-dependent kinase (CDK)-4 activity toward Rb. The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment, which also prevented the increase in cyclin D1 protein expression, CDK-4 activity, Rb phosphorylation, and the increase in UBF availability. Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is in part to modulate cyclin D1-dependent CDK-4 activity in the regulation of Rb and ribosomal RNA synthesis. On the basis of these results, we propose that common molecular mechanisms contribute to the regulation of myotube hypertrophy and growth during the G1 phase of the cell cycle.

scholarly journals Neuropeptide Y (NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation

2017 ◽  
Vol 312 (2) ◽  
pp. G103-G111 ◽  
Author(s):  
Sabrina Jeppsson ◽  
Shanthi Srinivasan ◽  
Bindu Chandrasekharan
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Neuropeptide Y ◽  
Intestinal Inflammation ◽  
Enteric Neurons ◽  
Intestinal Epithelial ◽  
Epithelial Proliferation ◽  
Proliferation And Apoptosis

We have demonstrated that neuropeptide Y (NPY), abundantly produced by enteric neurons, is an important regulator of intestinal inflammation. However, the role of NPY in the progression of chronic inflammation to tumorigenesis is unknown. We investigated whether NPY could modulate epithelial cell proliferation and apoptosis, and thus regulate tumorigenesis. Repeated cycles of dextran sodium sulfate (DSS) were used to model inflammation-induced tumorigenesis in wild-type (WT) and NPY knockout ( NPY−/−) mice. Intestinal epithelial cell lines (T84) were used to assess the effects of NPY (0.1 µM) on epithelial proliferation and apoptosis in vitro. DSS-WT mice exhibited enhanced intestinal inflammation, polyp size, and polyp number (7.5 ± 0.8) compared with DSS- NPY−/− mice (4 ± 0.5, P < 0.01). Accordingly, DSS-WT mice also showed increased colonic epithelial proliferation (PCNA, Ki67) and reduced apoptosis (TUNEL) compared with DSS- NPY−/− mice. The apoptosis regulating microRNA, miR-375, was significantly downregulated in the colon of DSS-WT (2-fold, P < 0.01) compared with DSS- NPY−/−-mice. In vitro studies indicated that NPY promotes cell proliferation (increase in PCNA and β-catenin, P < 0.05) via phosphatidyl-inositol-3-kinase (PI3-K)-β-catenin signaling, suppressed miR-375 expression, and reduced apoptosis (increase in phospho-Bad). NPY-treated cells also displayed increased c-Myc and cyclin D1, and reduction in p21 ( P < 0.05). Addition of miR-375 inhibitor to cells already treated with NPY did not further enhance the effects induced by NPY alone. Our findings demonstrate a novel regulation of inflammation-induced tumorigenesis by NPY-epithelial cross talk as mediated by activation of PI3-K signaling and downregulation of miR-375. NEW & NOTEWORTHY Our work exemplifies a novel role of neuropeptide Y (NPY) in regulating inflammation-induced tumorigenesis via two modalities: first by enhanced proliferation (PI3-K/pAkt), and second by downregulation of microRNA-375 (miR-375)-dependent apoptosis in intestinal epithelial cells. Our data establish the existence of a microRNA-mediated cross talk between enteric neurons producing NPY and intestinal epithelial cells, and the potential of neuropeptide-regulated miRNAs as potential therapeutic molecules for the management of inflammation-associated tumors in the gut.

Elevated protein expression of cyclin D1 and Fra-1 but decreased expression of c-Myc in human colorectal adenocarcinomas overexpressing ?-catenin

2002 ◽  
Vol 101 (4) ◽  
pp. 301-310 ◽  
Author(s):  
Hanlin L. Wang ◽  
Julia Wang ◽  
Shu-Yuan Xiao ◽  
Rex Haydon ◽  
Debra Stoiber ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Elevated Protein ◽  
Colorectal Adenocarcinomas
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