Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Gascoyne, Duncan M.; Hixon, Mary L.; Gualberto, Antonio; Vivanco, María dM

doi:10.4161/cc.2.3.355

Cited by 12 publications

(7 citation statements)

References 24 publications

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“…CKS1À/À knockout mice are unusually small and the cells derived from these mice proliferate slowly in association with the accumulation of p27Kip (Spruck et al, 2001). We observed overexpression of CKS1 in TOVs in tumor tissues, which correlates with the reported overexpression in colorectal (Shapira et al, 2004), gastric (Masuda et al, 2003), lung (Inui et al, 2003) and fibrosarcomas (Gascoyne et al, 2003). Together, results with CKS1 and CCNE1 suggest that the cell cycle can be targeted at different levels in EOC.…”

Section: Discussionsupporting

confidence: 74%

Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling

et al. 2005

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Tumors of low malignant potential (LMP) represent 20% of epithelial ovarian cancers (EOCs) and are associated with a better prognosis than the invasive tumors (TOV). Defining the relationship between LMPs and TOVs remains an important goal towards understanding the molecular pathways that contribute to prognosis, as well as providing molecular markers, for these EOCs. To this end, DNA microarray analyses were performed either in a primary culture or a tumor tissue model system and selected candidate genes showing a distinctive expression profile between LMPs and TOVs were identified using a class prediction approach based on three statistical methods of analysis. Both model systems appear relevant as candidate genes identified by either model allowed the proper reclassification of samples as either LMPs or TOVs. Selected candidate genes (CAS, CCNE1, LGALS8, ITGb3, ATP1B1, FLIP, KRT7 and KRT19) were validated by real-time quantitative PCR analysis and show differential expression between LMPs and TOVs. Immunohistochemistry analyses showed that the two tumor classes were distinguishable by their expression of CAS, TNFR1A, FLIP, CKS1 and CCNE1. These results define signature patterns for gene expression of LMPs and TOVs and identify gene candidates that warrant further study to deepen our understanding of the biology of EOC.

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Section: Discussionsupporting

confidence: 74%

Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling

et al. 2005

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“…Approximately 100,000 primary cells were FACS sorted and then cytospun on poly-lysine coated slides. Cell lines were grown directly on slides and processed as previously described [66]. Briefly, cells were fixed with 4% paraformaldehyde (Santa Cruz Biotech.…”

Section: Methodsmentioning

confidence: 99%

A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells

Domenici

Aurrekoetxea-Rodríguez

Simões

et al. 2019

Oncogene

125

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Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assays indicate that Sox9 is implicated in the maintenance of human breast luminal progenitor cells. CRISPR/Cas knockout of Sox9 reduces growth of tamoxifen-resistant breast tumours in vivo. Mechanistically, Sox9 acts downstream of Sox2 to control luminal progenitor cell content and is required for expression of the cancer stem cell marker ALDH1A3 and Wnt signalling activity. Sox9 is elevated in breast cancer patients after endocrine therapy failure. This new regulatory axis highlights the relevance of SOX family transcription factors as potential therapeutic targets in breast cancer.

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“…8,38 These two proteins have previously been implicated in different types of cancers. 15,[39][40][41][42][43] We observed increased expression of these two proteins in the higher-grade tumors. Cks1 is a sensitive marker for diagnosis and prognosis although its specificity remains low.…”

Section: Discussionmentioning

confidence: 99%

Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer

Ouellet

Guyot

Page

et al. 2006

Intl Journal of Cancer

118

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Molecular profiling is a powerful approach to identify potential clinical markers for diagnosis and prognosis as well as providing a better understanding of the biology of epithelial ovarian cancer. On the basis of the analysis of HuFL expression data, we have previously identified genes that distinguish low malignant potential and invasive serous epithelial ovarian tumors. In this study, we used immunohistochemistry to monitor a subset of differently expressed candidates (Ahr, Paep, Madh3, Ran, Met, Mek1, Ccne1, Ccd20, Cks1 and Cas). A tissue array composed of 244 serous tumors of different grades (0–3) and stages (I–IV) was used in this analysis. All markers assayed presented differential protein expression between serous tumors of low and high grade. Significant differences in Ccne1 and Ran expression were observed in a comparison of low malignant potential and grade 1 tumor samples (p < 0.01). In addition, irrespective of the grade, Ccne1, Ran, Cdc20 and Cks1 showed significant differences of expression in association with the clinical stage of disease. While high level of Ccne1 have previously been associated with poor outcomes, here we found that high level of either Ran or Cdc20 appear to be more tightly associated with a poor prognosis (p < 0.001, 0.03, respectively). The application of these biomarkers in both the initial diagnosis and prognostic attributes of patients with epithelial ovarian tumors should prove to be useful in patient management. © 2006 Wiley‐Liss, Inc.

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Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Cited by 12 publications

References 24 publications

Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling

Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling

A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells

Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer

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