Combined metallothioneins and p53 proteins expression as a prognostic marker in patients with Dukes stage B and C colorectal cancer

Bravo, I. Alda; Bruno, Lorenzo; Bayo, S. Morales; Hannois, Adrián; Loria, Fernando Sánchez; Pairola, F.; Huertas, Eduardo; Roberti, María Paula; Rocca, Yamila; Aris, Mariana; Barrio, María Marcela; Trasci, S. Baffa; Levy, Estrella Mariel; Mordoh, José; Bianchini, Michele

doi:10.1016/j.humpath.2011.12.014

Cited by 12 publications

(12 citation statements)

References 23 publications

(24 reference statements)

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“…As Pastuszewski et al (38), we also found remarkably higher MT-I/II expression in squamous cell laryngeal cancers than in hyperplastic lesions. The increase of MT-I/II expression was observed also in other cancers (63)(64)(65). In some cancers, the expression of MT-I/II correlates with the size of the tumour and the stage of the disease, as well as with resistance to chemotherapy and radiotherapy and poor prognosis for patients (35).…”

Section: Discussionmentioning

confidence: 91%

Correlation between levels of expression of minichromosome maintenance proteins, Ki-67 proliferation antigen and metallothionein I/II in laryngeal squamous cell cancer

Nowińska

Chmielewska

Piotrowska

et al. 2015

International Journal of Oncology

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MCM2, MCM3 and MCM7 are minichromosome maintenance proteins found in dividing cells and they play a role in DNA synthesis. Increased MCM expression level is observed in cells of different cancer types. Additionally, metallothioneins (MT-I/II) are involved in control of cell proliferation and differentiation and changes of their expression are observed in many types of cancer. Ki-67 is known cancer cell proliferation antigen currently used in prognostic evaluation. The study material consisted of 83 laryngeal squamous cell cancer (LSCC) cases and 10 benign hypertrophic lesions of larynx epithelium as a control group. For the present study, laryngeal cancer cell line HEp-2 and human keratinocytes were employed, and to evaluate expression of all the markers, immunohistochemical method (IHC), immunofluorescence (IF) and western blot analysis were used. Statistical analysis showed strong positive correlation between expression of MCM2, MCM3, MCM7 and Ki-67 antigen in LSCC. Additionally, moderate positive correlation was observed between MCM3 and MT-I/II expression. In cancer cells, the level of expression of MCM3, MCM2, MCM7 and Ki-67 markers was increasing with the grade of LSCC malignancy. IF and western blot analysis showed higher MCM2, MCM3, MCM7 expression in HEp-2 cells in comparison to their expression in keratinocytes. MCM proteins might be useful markers of cell proliferation in LSCC.

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Section: Discussionmentioning

confidence: 91%

Correlation between levels of expression of minichromosome maintenance proteins, Ki-67 proliferation antigen and metallothionein I/II in laryngeal squamous cell cancer

Nowińska

Chmielewska

Piotrowska

et al. 2015

International Journal of Oncology

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“…Cumulative reports have revealed that the expression of p53 is suppressed in cancer tissue [28]. The TP53 gene mutation is suggested as an important factor in the dysfunction of p53 that leads to tumorigenesis [11].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin ligase A20 regulates p53 protein in human colon epithelial cells

et al. 2013

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BackgroundIntestinal polyps may further develop into colon cancer; the pathogenesis is not clear. The p53 gene is an important anti-cancer gene in the body, which is suppressed in cancer. The ubiquitin E3 ligase A20 (A20) plays a role in regulating the activities of epithelial cells. This study was designed to investigate the role of the colon polyp epithelium-derived A20 in the pathogenesis of colon cancer.ResultsEighty-eight colon cancer patients and 136 colon polyp patients were recruited into this study. Human colon cancer tissue, the epithelium of adenomas polyp and hyperplastic polyp showed high levels of A20, which had a positive correlation with the cancerous tendency of colon polyps. The levels of A20 were much higher in the adenomas and hyperplastic polyps than that in the inflammatory polyps; the latter showed less cancerous tendency. A20 bound p53 to form complexes in colon cancer tissue and colon polyps. Over expression of A20 suppresses P53 protein levels in the HEK293 cells.ConclusionsA20 may play an important role in the cancerous tendency of colon polyposis.

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“…We and others have previously demonstrated that these proteins are progressively silenced during colorectal cancer progression, and that this is associated to poorer patient survival. (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy

Arriaga

Greco

Mordoh

et al. 2014

Molecular Cancer Therapeutics

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Metallothioneins (MT) are a family of low molecular weight proteins that are silenced during colorectal cancer progression, mainly through epigenetic mechanisms, and this loss is associated with poor survival. In this article, we show that overexpression of the MT1G isoform sensitizes colorectal cell lines to the chemotherapeutic agents oxaliplatin (OXA) and 5-fluorouracil (5-FU), in part through enhancing p53 and repressing NF-kB activity. Despite being silenced, MTs can be reinduced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate. In fact, this induction contributes to the cytotoxicity of these agents, given that silencing of MTs by siRNAs reduces their growth-inhibitory activities. Zinc ions also potently enhance MT expression and are cytotoxic to cancer cells. We show for the first time that OXA and 5-FU induce higher levels of intracellular labile zinc, as measured using the fluorescent probe FLUOZIN-3, and that such zinc contributes to the activation of p53 and repression of NF-kB. Addition of zinc enhanced growth inhibition by OXA and 5-FU, and was also capable of resensitizing 5-FU-resistant cell lines to levels comparable with sensitive cell lines. This effect was MT independent because silencing MTs did not affect zinc cytotoxicity. In conclusion, we show that MT induction and zinc administration are novel strategies to sensitize colorectal cancer cells to presently utilized chemotherapeutic agents. Mol Cancer Ther; 13(5); 1369-81. Ó2014 AACR.

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Combined metallothioneins and p53 proteins expression as a prognostic marker in patients with Dukes stage B and C colorectal cancer

Cited by 12 publications

References 23 publications

Correlation between levels of expression of minichromosome maintenance proteins, Ki-67 proliferation antigen and metallothionein I/II in laryngeal squamous cell cancer

Correlation between levels of expression of minichromosome maintenance proteins, Ki-67 proliferation antigen and metallothionein I/II in laryngeal squamous cell cancer

Ubiquitin ligase A20 regulates p53 protein in human colon epithelial cells

Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy

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