Tumor-specific hyperactive low-molecular-weight cyclin E isoform detection and characterization in non-metastatic colorectal tumors

Corin, Irina; Giacomo, Marilena Carmela Di; Lastella, Patrizia; Bagnulo, Rosanna; Guanti, Ginevra; Simone, Cristiano

doi:10.4161/cbt.5.2.2356

Cited by 27 publications

(22 citation statements)

References 32 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HT29, SW480, Hct116 and Caco2 cells were cultured as described. 40 LS174T, Hep3B, HeLa, HEK293, C2C12, CH310T1/2, NIH3T3 and RD cells were maintained in DMEM with 10% FBS. hFSF were isolated and cultured as described.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

et al. 2006

View full text Add to dashboard Cite

Cancer develops when molecular pathways that control the fine balance between proliferation, differentiation, autophagy and cell death undergo genetic deregulation. The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of these pathways in tumor cells. In an effort to evaluate the impact of p38 signaling on colorectal cancer cell fate, we treated HT29, Caco2, Hct116, LS174T and SW480 cell lines with the inhibitor SB202190 specific for p38a/b kinases. We report that p38a is required for colorectal cancer cell homeostasis as the inhibition of its kinase function by pharmacological blockade or genetic inactivation causes cell cycle arrest, autophagy and cell death in a cell type-specific manner. Deficiency of p38a activity induces a tissue-restricted upregulation of the GABARAP gene, an essential component of autophagic vacuoles and autophagosomes, whereas simultaneous inhibition of autophagy significantly increases cell death by triggering apoptosis. These data identify p38a as a central mediator of colorectal cancer cell homeostasis and establish a rationale for the evaluation of the pharmacological manipulation of the p38a pathway in the treatment of colorectal cancer. Colorectal cancer is a major health concern, with more than 1 000 000 new cases and 500 000 deaths expected worldwide per year.1 Prognostic evaluation is currently based on histological appearance, and there are no molecular markers internationally recognized as standard predictor factors. The conventional therapy involving surgery and adjuvant therapy seems to give rise to improvements in progression-free and overall survival. Nevertheless about 50% of patients die within 5 years owing to metastasis or recurrent disease.2 The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of cell cycle and cell death regulatory pathways in tumor cells in order to identify differential cellular effects of agents that may have a direct impact on cancer therapy.During the last decade, a number of deacetylase inhibitors (DI) have been identified. These DI induce tumor cells to undergo growth arrest, differentiation, and/or apoptosis in culture and in animal models, at doses that seem to be nontoxic and appear to be selective. Butyrate, a DI that is naturally formed in the human colon, is able to reduce the size and the number of tumors in rat models of bowel cancer.3 In vitro, sodium butyrate (NaB) is a potent differentiating agent for several colorectal cancer cell lines (CRCs).4-6 NaB-mediated cell cycle withdrawal of CRCs appears to be dependent on acetylation of histones and consequent changes in transcription, requiring continuous protein synthesis and the expression of p21. 7 It has recently been shown that 1 mM NaB is the best working concentration to activate the differentiation program in CRCs without triggering apoptosis, whereas 5 mM NaB is sufficient to induce a p53-independent...

show abstract

Section: Methodsmentioning

confidence: 99%

“…hFSF were isolated and cultured as described. 40 The proliferation, viability and cell death of the reported cell lines were scored by cell counting. Briefly, at the indicated time points the supernatants (containing dead/floating cells) were collected, and the remaining adherent cells were detached with Trypsin/EDTA.…”

Section: Methodsmentioning

confidence: 99%

A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Overexpression of cyclins and CDKs and loss of expression of CKIs (CDK inhibitors) are frequently reported in human neoplasia. The overexpression of cyclin E is common in various types of cancer, including breast cancer, 3,4 nonsmall cell lung cancer (NSCLC), 5,6 colon cancer, 7 bladder cancer, 8 and ovarian cancer. 9 Cancers of the digestive system are common worldwide, while the pattern and incidence vary widely between different parts of the world.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Expression of Cyclin E in Gastrointestinal Cancer

Huang

Ren

Tang

et al. 2015

Technol Cancer Res Treat

View full text Add to dashboard Cite

Cyclin E is a critical regulator in cell cycle and promotes the initiation of DNA replication and centrosome duplication in late G1. The overexpression of cyclin E is common in cancers of the digestive system. However, whether cyclin E represents a prognostic biomarker in gastrointestinal cancer remains controversial. We reviewed the published literatures to clarify the association between cyclin E determined by immunohistochemistry (IHC) and survival in gastrointestinal cancer. Literatures were searched in PubMed and Cochrane Library published up to December 1, 2014. A total of 282 articles were initially identified, and 14 articles were included in this study. Meta-analysis was performed for 10 studies with a total of 1300 patients. Combined hazard risk (HR) and corresponding 95% confidence interval (CI) were calculated by random-effect model due to the heterogeneity. The quality of included studies was assessed by the Newcastle-Ottawa Scale and the Methodological Index for Non-Randomized Studies (MINORS). We found that high level of cyclin E was a predicator of poor prognosis among patients with gastrointestinal cancer (HR ¼ 1.67, 95% CI ¼ 1.06-2.63, P ¼ .028). In summary, overexpression of cyclin E is associated with poor prognosis in gastrointestinal cancer and expression of cyclin E determined by IHC might be a prognostic marker for gastrointestinal cancer in clinical practice.

show abstract

“…21e23 These isoforms are also found in ovarian cancer, 4,24 melanomas, 2 gastric cancer, 25 colorectal cancer, 26e28 lung cancer, 29 and renal cell carcinomas 30 and are strongly associated with poor survival in patients. 4,26,31 Work from our laboratory has implicated LMW-E in breast cancer oncogenesis. For example, LMW-E i) is biochemically hyperactive because of its increased affinity for cdk2 and resistance to inhibition by the CDK inhibitors p21 and p27 32 ; ii) is resistant to the growth-inhibiting effects of antiestrogens 33 and aromatase inhibitors 34 ; iii) promotes deregulation of cell cycle, 35 centrosome amplification, 13 and genomic instability 33 ; iv) causes premature inactivation of Cdc25C and PLK1, leading to faster mitotic exit 16 ; v) is sufficient to render human mammary epithelial cells tumorigenic and leads to altered acinar morphogenesis 36 ; vi) phosphorylates Hbo1 to mediate a cancer stem cell-like environment 14 ; and vii) is a downstream oncogenic target of protein kinase Ci.…”

mentioning

confidence: 99%

Cytoplasmic Cyclin E and Phospho–Cyclin-Dependent Kinase 2 Are Biomarkers of Aggressive Breast Cancer

Karakaş

Biernacka

Bui

et al. 2016

The American Journal of Pathology

View full text Add to dashboard Cite

Cyclin E and its co-activator, phosphoecyclin-dependent kinase 2 (p-CDK2), regulate G 1 to S phase transition and their deregulation induces oncogenesis. Immunohistochemical assessments of these proteins in cancer have been reported but were based only on their nuclear expression. However, the oncogenic forms of cyclin E (low molecular weight cyclin E or LMW-E) in complex with CDK2 are preferentially mislocalized to the cytoplasm. Here, we used separate nuclear and cytoplasmic scoring systems for both cyclin E and p-CDK2 expression to demonstrate altered cellular accumulation of these proteins using immunohistochemical analysis. We examined the specificity of different cyclin E antibodies and evaluated their concordance between immunohistochemical and Western blot analyses in a panel of 14 breast cell lines. Nuclear versus cytoplasmic staining of cyclin E readily differentiated fulllength from LMW-E, respectively. We also evaluated the expression of cyclin E and p-CDK2 in 1676 breast carcinoma patients by immunohistochemistry. Cytoplasmic cyclin E correlated strongly with cytoplasmic p-CDK2 (P < 0.0001), high tumor grade, negative estrogen/progesterone receptor status, and human epidermal growth factor receptor 2 positivity (all P < 0.0001). In multivariable analysis, cytoplasmic cyclin E plus phosphorylated CDK2 (as one variable) predicted breast cancer recurrence-free and overall survival. These results suggest that cytoplasmic cyclin E and p-CDK2 can be readily detected with immunohistochemistry and used as clinical biomarkers for aggressive breast cancer. (Am J Pathol 2016 http://dx

show abstract

Tumor-specific hyperactive low-molecular-weight cyclin E isoform detection and characterization in non-metastatic colorectal tumors

Cited by 27 publications

References 32 publications

A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

Prognostic Value of Expression of Cyclin E in Gastrointestinal Cancer

Cytoplasmic Cyclin E and Phospho–Cyclin-Dependent Kinase 2 Are Biomarkers of Aggressive Breast Cancer

Contact Info

Product

Resources

About