Interplay of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-I Receptor, COX-2, and Matrix Metalloproteinase-7, Play Key Roles in the Early Stage of Colorectal Carcinogenesis

Nosho, Katsuhiko; Yamamoto, Hiroyuki; Taniguchi, Hiroaki; Adachi, Yasushi; Yoshida, Yukinari; Arimura, Yoshiaki; Endo, Takao; Hinoda, Yuji; Imai, Kohzoh

doi:10.1158/1078-0432.ccr-04-0875

Cited by 51 publications

(48 citation statements)

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“…In this study, the expression of total mRNA and all splicing isoforms of IGF-1 mRNA was observed in all the examined CRC and control samples. Existing data on the detection of IGF-1 mRNA vary between the absence of the transcript in CRC tissue (46), HT-29 and CaCo-2 cells (47), its detection in a proportion of cases (41-54% in CRC and 60-67% in control samples) (47)(48)(49) to its demonstration in all (100%) CRC and normal colon samples (50), which was supported by our results.…”

Section: Discussionsupporting

confidence: 89%

“…Nosho et al applied qPCR as we did, and demonstrated IGF-1 mRNA overexpression in ~54% of 90 human colorectal tumor tissues (49). The transcript was only faintly detected in adjacent non-tumor tissues.…”

Section: Discussionsupporting

confidence: 54%

“…Studies on the level of IGF-1 mRNA expression which were obtained using various quantitative molecular techniques in CRC have also reported variable results (46,(49)(50)(51). The lack of differences in the expression levels of IGF-1 mRNA in 10 colorectal sporadic cancers (Dukes' stage B or C) as well as in the epithelium scraped from normal colon mucosa was revealed by Michell et al using northern and western blot analysis (50).…”

Section: Discussionmentioning

confidence: 99%

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Differential expression of IGF-1 mRNA isoforms in colorectal carcinoma and normal colon tissue

et al. 2012

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Abstract. The insulin-like growth factor (IGF)-1 gene consists of 6 exons resulting in the expression of 6 variant forms of mRNA (IA, IB, IC, IIA, IIB and IIC) due to an alternative splicing. The mechanisms of IGF-1 gene splicing and the role of local expression manifested by IGF-1 mRNA variants in colorectal carcinoma (CRC) have not been extensively investigated. Therefore, the aim of our study was to analyse the expression of IGF-1 mRNA isoforms [A, B, C, P1 (class I) and P2 (class II)], as well as the protein expression in CRC and control samples isolated from 28 patients. The expression of Ki-67 was also analysed and clinical data were obtained. For this purpose, we used quantitative real-time PCR (qPCR) and immunocytochemistry. The expression of mRNAs coding for all splicing isoforms of IGF-1 was observed in every tissue sample studied, with a significantly lower expression noted in the CRC as compared to the control samples. The cytoplasmic expression of IGF-1 protein was found in 50% of the CRC and in ~40% of the non-tumor tissues; however, no significant quantitative inter-group differences were observed. The expression of the IGF-1 gene in the 2 groups of tissues was controlled by the P1 and P2 promoters in a similar manner. No significant differences were detected in the expression of the IGF-1 A and B isoforms; however, their expression was significantly higher compared to that of isoform C. No significant differences were observed between the expression of Ki-67 mRNA in the CRC and control tissue even though the expression of the Ki-67 protein was higher in the CRC compared to the control samples. Ki-67 protein expression was associated with the macroscopic and microscopic aspects of CRC. A significant positive correlation was found between the local production of total mRNA and isoform A and the expression of Ki-67 mRNA, although only in the non-tumor tissues. In CRC samples, the local expression of the total IGF-1 mRNA and all splicing isoforms of IGF-1 mRNA decreased as compared to the normal colon tissues, although however, with conservation of both gene promoter activities and with the continued principal splicing IGF-1 mRNA isoforms.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

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Differential expression of IGF-1 mRNA isoforms in colorectal carcinoma and normal colon tissue

et al. 2012

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“…IGF-II mRNA expression was undetectable or only faintly detectable in adjacent nontumor tissue. In 6 of 7 patients with carcinomas arising in adenomas, IGF-II mRNA expression in the carcinoma was >10 times higher than in the adenoma portion of the lesion by complimentary DNA (cDNA) array analysis and IHC [14].…”

Section: Laboratory Studiesmentioning

confidence: 98%

“…In an analysis of IGF-I, IGF-II, IGF-1R, COX-2, and MMP-7 expression in 90 human colorectal tumors (63 adenomas and 27 submucosal pT1 cancers), IGF-II was also found to be the most differentially expressed gene between carcinoma and adenoma lesions [14]. Semiquantitative RT-PCR was used to detect gene expression.…”

Section: Laboratory Studiesmentioning

confidence: 99%

Role of insulin-like growth factor-1R system in colorectal carcinogenesis

Donovan

Kummar

2008

Critical Reviews in Oncology/Hematology

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The insulin-like growth factor (IGF) system is comprised of receptors, ligands (IGF-I and IGF-II), and a family of binding proteins (IGFBPs). It plays an important role in growth and development and in the maintenance of normal homeostasis. We present a review of the current laboratory and epidemiologic evidence that suggests an important role of the IGF system in colorectal carcinogenesis. Due to the complexity of this system, we have focused the review on the role of the IGF-1 receptor and its ligands in colorectal carcinogenesis and the strategies to block this pathway as a potential anti-cancer therapy.

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The effect of forced expression of mutated K‐RAS gene on gastrointestinal cancer cell lines and the IGF‐1R targeting therapy

Matsunaga

Adachi

Sasaki

et al. 2016

Molecular Carcinogenesis

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Mutation in K-RAS (K-RAS-MT) plays important roles in both cancer progression and resistance to anti-epidermal growth factor receptor (EGFR) therapy in gastrointestinal tumors. Insulin-like growth factor-1 receptor (IGF-1R) signaling is required for carcinogenicity and progression of many tumors as well. We have previously shown successful therapy for gastrointestinal cancer cell lines bearing a K-RAS mutation using an anti-IGF-1R monoclonal antibody. In this study, we sought to evaluate effects of forced K-RAS-MT expression on gastrointestinal cancer cell lines representing a possible second resistance mechanism for anti-EGFR therapy and IGF-1R-targeted therapy for these transfectants. We made stable transfectants of K-RAS-MT in two gastrointestinal cancer cell lines, colorectal RKO and pancreatic BxPC-3. We assessed the effect of forced expression of K-RAS-MT on proliferation, apoptosis, migration, and invasion in gastrointestinal cancer cells. Then we assessed anti-tumor effects of dominant negative IGF-1R (IGF-1R/dn) and an IGF-1R inhibitor, picropodophyllin, on the K-RAS-MT transfectants. Overexpression of K-RAS-MT in gastrointestinal cancer cell lines led to more aggressive phenotypes, with increased proliferation, decreased apoptosis, and increased motility and invasion. IGF-1R blockade suppressed cell growth, colony formation, migration, and invasion, and up-regulated chemotherapy-induced apoptosis of gastrointestinal cancer cells, even when K-RAS-MT was over-expressed. IGF-1R blockade inhibited the Akt pathway more than the extracellular signal-regulated kinase (ERK) pathway in the K-RAS-MT transfectants. IGF-1R/dn, moreover, inhibited the growth of murine xenografts expressing K-RAS-MT. Thus, K-RAS-MT might be important for progressive phonotype observed in gastrointestinal cancers. IGF-1R decoy is a candidate molecular therapeutic approach for gastrointestinal cancers even if K-RAS is mutated. © 2016 Wiley Periodicals, Inc.

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Interplay of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-I Receptor, COX-2, and Matrix Metalloproteinase-7, Play Key Roles in the Early Stage of Colorectal Carcinogenesis

Abstract: ABSTRACT

Cited by 51 publications

References 46 publications

Differential expression of IGF-1 mRNA isoforms in colorectal carcinoma and normal colon tissue

Differential expression of IGF-1 mRNA isoforms in colorectal carcinoma and normal colon tissue

Role of insulin-like growth factor-1R system in colorectal carcinogenesis

The effect of forced expression of mutated K‐RAS gene on gastrointestinal cancer cell lines and the IGF‐1R targeting therapy

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