A study of the expression of Cyclin E and its isoforms in tumor and adjacent mucosa, correlated to patient outcome in early colon cancer

Corin, Irina; Larsson, Lisa; Bergström, Jakob; Gustavsson, Bengt; Derwinger, Kristoffer

doi:10.3109/02841860903268049

Cited by 16 publications

(11 citation statements)

References 20 publications

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“…[16][17][18][19][20] These proteins are confirmed to participate in the regulation of cell cycle, apoptosis or tumor invasion, and metastasis. Our results show that the proteins in necroptosis play an important role in determining tumor cell death and whether it can benefit from chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Association of Mixed Lineage Kinase Domain-Like Protein Expression With Prognosis in Patients With Colon Cancer

Guo

An-wei

et al. 2016

Technol Cancer Res Treat

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Background: The mixed lineage kinase domain-like protein has recently been identified as a key downstream component of tumor necrosis factor-induced necroptosis, which is an important pathway of cancer cell death. The goal of the current study is to explore the expression of mixed lineage kinase domain-like protein in colon cancer tissues and evaluate the prognostic value in patients with colon cancer. Methods: We collected normal and cancer colon tissues from 135 patients diagnosed with colon cancer after radical operation during July 2007 to April 2009 at The Affiliated Hospital of Qingdao University. Immunohistochemistry analysis was scored using an established scoring system. Kaplan-Meier survival curves were generated for recurrence-free survival and overall survival for all patients and 2 subsets of patients. The relationship between mixed lineage kinase domain-like protein expression and prognosis parameter (recurrence-free survival, overall survival) was analyzed by univariate and multivariate Cox regression analyses. Results: The median age of all patients was 67 years and 56.3% were male. Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (78.6 vs 81.2 months; P ¼ .011) in all patients. In the subset of 79 patients who received adjuvant chemotherapy, low expression of mixed lineage kinase domain-like protein was associated with decreased recurrence-free survival (60.4 vs 72.8 months; P ¼ .032) and decreased overall survival (66.3 vs 72.9 months; P ¼ .005). Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (74.9 vs 79.8 months; P ¼ .006) and recurrence-free survival (69.6 vs 78.8 months; P ¼ .005) among patients with Tumor Node Metastasis (TNM) stage II colon cancer. Conclusions: Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival in all patient-group with resected colon cancer. It is associated with decreased recurrencefree survival and overall survival in the subset of patients who receive adjuvant chemotherapy and patients who were TNM stage II. Mixed lineage kinase domain-like protein may provide important prognostic information in patients with colon cancer.

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Section: Discussionmentioning

confidence: 99%

Association of Mixed Lineage Kinase Domain-Like Protein Expression With Prognosis in Patients With Colon Cancer

Guo

An-wei

et al. 2016

Technol Cancer Res Treat

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“…Although the full-length (FL) Cyclin E1 isoform, termed El1, is detected in normal and malignant cells (1), overexpression of up to five low-molecular-weight (LMW) Cyclin E1 isoforms has been reported in malignant tissues (2)(3)(4). Amino-terminal truncated isoforms El2/3 and El5/6 arise by proteolytic cleavage of the FL protein by Elastase (5) or Calpain 2 (6) proteases.…”

Section: Introductionmentioning

confidence: 99%

Defective Myb Function Ablates Cyclin E1 Expression and Perturbs Intestinal Carcinogenesis

Cheasley

Pereira

Sampurno

et al. 2015

Molecular Cancer Research

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Cyclin E1 is essential for the reentry of quiescent cells into the cell cycle. When hypomorphic mutant Myb mice (Myb Plt4 ) were examined, it was noted that Cyclin E1 (Ccne1) expression was reduced. Furthermore, the induction of Ccne1 in recovering intestinal epithelia following radiation-induced damage was ablated in Myb-mutant mice. These data prompted us to investigate whether Myb directly regulated Ccne1 and to examine whether elevated Myb in colorectal cancer is responsible for Cyclin E1-driven tumor growth. Here, it was found that Myb/ MYB and Ccne1/CCNE1 expressions were coupled in both mouse and human adenomas. In addition, the low molecular weight Cyclin E1 was the predominant form in intestinal crypts and adenomatous polyposis coli (Apc)-mutant adenomas. Chromatin immunoprecipitation (ChIP) analysis confirmed that Myb bound directly to the Ccne1 promoter and regulated its endogenous expression. In contrast, Myb Plt4 served as a dominant-negative factor that inhibited wild-type Myb and this was not apparently compensated for by the transcription factor E2F1 in intestinal epithelial cells. Myb Plt4/Plt4 mice died prematurely on an Apc Min/þ background associated with hematopoietic defects, including a myelodysplasia; nevertheless, Apc Min/þ mice were protected from intestinal tumorigenesis when crossed to Myb Plt4/þ mice. Knockdown of CCNE1 transcript in murine colorectal cancer cells stabilized chromosome ploidy and decreased tumor formation. These data suggest that Cyclin E1 expression is Myb dependent in normal and transformed intestinal epithelial cells, consistent with a cell-cycle progression and chromosome instability role in cancer.Implications: This study demonstrates that Myb regulates Cyclin E1 expression in normal gastrointestinal tract epithelial cells and is required during intestinal tumorigenesis. Mol Cancer Res; 13(8); 1185-96. Ó2015 AACR.

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“…The detection of such markers may aid in risk stratification and cyclin E may be included in the list of possible candidates. The role of cyclin E in colon tumorgenesis is supported by certain studies which revealed overexpression of cyclin E in early stages of tumor development (17,23). Positive cyclin E staining was correlated with Ki-67 antigen (a marker of proliferative activity of malignant cells) and p53 protein level in these cells (3,24).…”

Section: A B Cmentioning

confidence: 69%

“…Increased levels of cyclin E in certain cases indicate gene amplification (25,26). Corin et al revealed a significant correlation between high total cyclin E expression and cancer-specific survival in patients with colon cancer (17). Zhou et al found that cyclin E overexpression is a strong negative predictor for survival in patients with rectal cancer (27).…”

Section: A B Cmentioning

confidence: 99%

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Expression of cyclin E in stage III colorectal carcinoma

et al. 2012

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Abstract. Carcinogenesis is characterized by an abnormal regulation of the cell cycle. Regulators of the cell cycle such as cyclin E play an important role in neoplasia and may be correlated with prognosis. The clinical significance of the expression of cyclin E in stage III colorectal carcinoma has not yet been investigated. The expression of cyclin E was evaluated in 49 patients. Using a multivariate analysis, the expression of cyclin E in the tumor at diagnosis was compared with various clinicopathological variables, including age, gender, tumor site, tumor size, tumor differentiation and lymph node involvement. There were more node-positive cases in the cyclin E-negative group than in the cyclin E-positive group (P=0.003). However, there was no correlation between the degree of cyclin E expression and the clinical data. In conclusion, our data suggest that overexpression of cyclin E does not predict the clinical outcome in colorectal cancer stage III. Negative cyclin E staining may be associated with lymph node involvement.

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A study of the expression of Cyclin E and its isoforms in tumor and adjacent mucosa, correlated to patient outcome in early colon cancer

Cited by 16 publications

References 20 publications

Association of Mixed Lineage Kinase Domain-Like Protein Expression With Prognosis in Patients With Colon Cancer

Association of Mixed Lineage Kinase Domain-Like Protein Expression With Prognosis in Patients With Colon Cancer

Defective Myb Function Ablates Cyclin E1 Expression and Perturbs Intestinal Carcinogenesis

Expression of cyclin E in stage III colorectal carcinoma

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