Immunohistochemical analysis of IQGAP1 expression in human colorectal carcinomas: its overexpression in carcinomas and association with invasion fronts

Nabeshima, Kazuki; Shimao, Yoshiya; Inoue, Teruhiko; Koono, Masashi

doi:10.1016/s0304-3835(01)00742-x

Cited by 113 publications

(95 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Its role in carcinogenesis has already been reported, 23 and it has been mentioned that IQGPA1 might be involved in gastric and colorectal cancers. 24,25 Figure 1 Overall analysis of the WTCCC data. Quantile -quantile plots of the test statistic observed in the seven studied diseases.…”

Section: Resultsmentioning

confidence: 99%

Using biological networks to search for interacting loci in genome-wide association studies

et al. 2009

View full text Add to dashboard Cite

Genome-wide association studies have identified a large number of single-nucleotide polymorphisms (SNPs) that individually predispose to diseases. However, many genetic risk factors remain unaccounted for. Proteins coded by genes interact in the cell, and it is most likely that certain variants mainly affect the phenotype in combination with other variants, termed epistasis. An exhaustive search for epistatic effects is computationally demanding, as several billions of SNP pairs exist for typical genotyping chips. In this study, the experimental knowledge on biological networks is used to narrow the search for two-locus epistasis. We provide evidence that this approach is computationally feasible and statistically powerful. By applying this method to the Wellcome Trust Case -Control Consortium data sets, we report four significant cases of epistasis between unlinked loci, in susceptibility to Crohn's disease, bipolar disorder, hypertension and rheumatoid arthritis.

show abstract

Section: Resultsmentioning

confidence: 99%

Using biological networks to search for interacting loci in genome-wide association studies

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In colorectal cancer, overexpression of IQGAP1 in carcinomas and its association with invasion fronts has been detected. 26 In ovarian cancer, overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters. 27 To conclude, these reports and our own results converge at a negative role for IQGAP1 in tumorigenesis.…”

Section: The Rac1 Downstream Effector Iqgap1mentioning

confidence: 99%

Combined analysis of Rac1, IQGAP1, Tiam1 and E-cadherin expression in gastric cancer

et al. 2008

View full text Add to dashboard Cite

Rho GTPases are a family of major regulators of E-cadherin-mediated cell adhesion that are implicated in the carcinogenic process by deregulated expression of the family members itself or of upstream modulators or downstream effectors. Combined investigation of the Rho GTPase Rac1, the effector protein IQGAP1 and the activator Tiam1 in relation to expression or mutation of E-cadherin in gastric adenocarcinomas has not been reported. The aim of the study was to determine the expression and prognostic significance of Rac1, IQGAP1, Tiam1 and E-cadherin in gastric adenocarcinomas. Gastric carcinomas of 76 patients were investigated immunohistochemically in a tissue microarray study for expression of Rac1, IQGAP1, Tiam1 and E-cadherin. Correlations with clinical and follow-up data were examined. Moderate or strong reactivity for Rac1 was observed in 46% and for Tiam1 in 56% of tumors. Expression of IQGAP1 was present in 59% and of E-cadherin in 87% of tumors. While Rac1 and E-cadherin expression were not related to prognosis, a trend was observed between a lack of IQGAP1 expression (log-rank 0.088) as well as presence of Tiam1 (log-rank 0.097) and favorable prognosis in Kaplan-Meier survival analysis. Expression of Rac1 was positively linked to IQGAP1 expression (P ¼ 0.007, r ¼ 0.343) and tended to be inversely associated with expression of E-cadherin (P ¼ 0.055, r ¼ À0.245). In conclusion, we observed deregulated expression of Rac1, IQGAP1, Tiam1 and E-cadherin in gastric cancer. We present evidence that either upregulation (for Rac1 and IQGAP1) or downregulation (for Tiam1 and E-cadherin) occurs. Rac1 and E-cadherin expression were not related to prognosis, while trends pointing to favorable prognosis of patients with Tiam1 expression and a lack of IQGAP1 expression were observed. These results indicate that the investigated regulators of E-cadherin-mediated cell adhesion play a role in gastric carcinogenesis.

show abstract

“…Proprotein convertases (PCs) process latent precursor proteins into their biologically active products, including protein tyrosine phosphatases, growth factors and their receptors, and enzymes like matrix metalloproteases (MMPs), and thus may have a functional role in the tumour cell invasion and tumour progression. Other upregulated genes encoded various signalling proteins including PRAME, an interactor of the cytoskeleton-regulator paxillin, IQ-GAP1, a negative regulator of the E-cadherin/catenin complex-based cell-cell adhesion (Nabeshima et al, 2002), LTPB4, a structural component of connective tissue microfibrils and local regulator of TGFb tissue deposition and signalling (Sterner-Kock et al, 2002), and IGF1R1. IGF1R has been recently shown to be involved in metastases of CRC by preventing apoptosis, enhancing cell proliferation and inducing angiogenesis (Reinmuth et al, 2002).…”

Section: Expression Profiles and Clinical Outcomementioning

confidence: 99%

Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters

et al. 2004

View full text Add to dashboard Cite

Different diagnostic and prognostic groups of colorectal carcinoma (CRC) have been defined. However, accurate diagnosis and prediction of survival are sometimes difficult. Gene expression profiling might improve these classifications and bring new insights into underlying molecular mechanisms. We profiled 50 cancerous and noncancerous colon tissues using DNA microarrrays consisting of B8000 spotted human cDNA. Global hierarchical clustering was to some extent able to distinguish clinically relevant subgroups, normal versus cancer tissues and metastatic versus nonmetastatic tumours. Supervised analyses improved these segregations by identifying sets of genes that discriminated between normal and tumour tissues, tumours associated or not with lymph node invasion or genetic instability, and tumours from the right or left colon. A similar approach identified a gene set that divided patients with significantly different 5-year survival (100% in one group and 40% in the other group; P ¼ 0.005). Discriminator genes were associated with various cellular processes. An immunohistochemical study on 382 tumour and normal samples deposited onto a tissue microarray subsequently validated the upregulation of NM23 in CRC and a downregulation in poor prognosis tumours. These results suggest that microarrays may provide means to improve the classification of CRC, provide new potential targets against carcinogenesis and new diagnostic and/or prognostic markers and therapeutic targets.

show abstract

Immunohistochemical analysis of IQGAP1 expression in human colorectal carcinomas: its overexpression in carcinomas and association with invasion fronts

Cited by 113 publications

References 24 publications

Using biological networks to search for interacting loci in genome-wide association studies

Using biological networks to search for interacting loci in genome-wide association studies

Combined analysis of Rac1, IQGAP1, Tiam1 and E-cadherin expression in gastric cancer

Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters

Contact Info

Product

Resources

About