Expression of insulin-like growth factor 2 mRNA in human gastric cancer.

Shiraishi, Takeshi; Mori, Masaki; Yamagata, Motoyuki; Haraguchi, Masanobu; Ueo, Hiroaki; Sugimachi, Keizō

doi:10.3892/ijo.13.3.519

Cited by 17 publications

(19 citation statements)

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“…IGF-II expression was increased in prostate cancer when compared with nonmalignant prostate tissues (16,17), and the increased expression was associated with prostate cancer progression (18). High levels of IGF-II expression were also found in breast cancer (19,20), gastric cancer (21,22), and esophageal cancer (23). In colorectal cancer, both IGF-II mRNA and protein were shown to be elevated compared with normal tissue, and the elevation was associated with advanced disease stage and poor prognosis (24 -26).…”

Section: Discussionmentioning

confidence: 81%

The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer.

Katsaros

Wiley

et al. 2006

Clinical Cancer Research

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Purpose: The insulin-like growth factor (IGF) system plays important roles in cancer; blocking IGF signaling has been shown to have therapeutic effects on tumor growth. Many studies have focused on the effect of IGF-I, but few have addressed IGF-II.To assess the role of IGF-II in cancer, we analyzed IGF-II expression in ovarian cancer and examined its association with disease characteristics and prognosis. Experimental Design: Included in the study were 215 patients with primary epithelial ovarian cancer. Fresh tumor specimens were collected during surgery, and the patients were followed for a median of 31 months. Total RNA was extracted from the tumor and analyzed for IGF-II, IGF binding protein 3 (IGFBP-3), and estrogen receptor-a expressions using quantitative reverse transcription PCR. Survival analysis was done to examine the associations of IGF-II with disease progression. Results: IGF-II expression was found to be higher in tumors with poor prognosis; this included tumors with advanced stage, poor differentiation, serous histology, and large residual lesions. Patients with high IGF-II had elevated risk for disease progression and death, although the significance became less evident when the analysis was adjusted for clinical and pathologic variables. IGFBP-3 expression was higher in less aggressive tumors, but was not associated with disease progression. The expression of estrogen receptor-a had no effect on survival. Conclusion:This study found evidence that IGF-II expression is associated with disease progression, suggesting that IGF-II and IGF signaling are potential targets for ovarian cancer treatment. The study also indicates that IGF-II and IGFBP-3 have limited value in prognosis because of their strong associations with disease stage and tumor grade.

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Section: Discussionmentioning

confidence: 81%

The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer.

Katsaros

Wiley

et al. 2006

Clinical Cancer Research

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“…The IGF-II gene plays an important role in lymph vessel permeation especially in expanding-type gastric cancers (Shiraishi et al, 1998). Pavelic and colleagues (Pavdic et al, 2003) have reported that increased expression of IGF-II and IGF-IR genes is found in gastric cancer as compared with non-tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

PTEN/MMAC1 enhances the growth inhibition by anticancer drugs with downregulation of IGF-II expression in gastric cancer cells

Hwang

Kim²,

Lee³

et al. 2005

Exp Mol Med

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“…When control cells of 44As3 miLacZ or NKPS miLacZ were injected intraperitoneally into nude mice, severe carcinomatous perito- VOL. 29,2009 C9orf10 REGULATES Src FAMILY KINASES 409…”

Section: Resultsmentioning

confidence: 99%

“…Further experiments should be conducted to determine (i) whether Ossa and IMP-1 modify each other's functions and (ii) their biological significance in cancer progression. Elevated expression of IGF-II is often observed in human gastric cancer tissues, especially in the infiltrative-type cancers (29), and the paracrine or autocrine pathway of IGF-II causes a significant increase in the PI3-kinase and Akt pathway, which rescues cells from apoptosis (5). It was reported previously that cross talk occurs between SFKs and a factor that mediates nucleic acid-directed processes, a Src-associated substrate during mitosis, the 68-kDa protein Sam68, which belongs to the family of KH domain-containing RNA-binding proteins, and that its tyrosine phosphorylation via interaction with SFKs causes a decreased affinity for RNA (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…We showed that Ossa functions as a scaffolding protein for SFK and PI3-kinase, which enables SFK to VOL. 29,2009 C9orf10 REGULATES Src FAMILY KINASES 411 phosphorylate and activate PI3-kinase. Such direct activation of PI3-kinase by SFK was supported by a previous report that incubation of purified p85/p110 with Src activated PI3-kinase activity in vitro (2).…”

Section: Discussionmentioning

confidence: 99%

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A Novel RNA-Binding Protein, Ossa/C9orf10, Regulates Activity of Src Kinases To Protect Cells from Oxidative Stress-Induced Apoptosis

Tanaka¹,

Sasaki

Kamata³

et al. 2009

Molecular and Cellular Biology

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During the process of tumor progression and clinical treatments, tumor cells are exposed to oxidative stress. Tumor cells are frequently resistant to such stress by producing antiapoptotic signaling, including activation of Src family kinases (SFKs), although the molecular mechanism is not clear. In an attempt to identify the SFK-binding proteins selectively phosphorylated in gastric scirrhous carcinoma, we identified an uncharacterized protein, C9orf10. Here we report that C9orf10 (designated Ossa for oxidative stressassociated Src activator) is a novel RNA-binding protein that guards cancer cells from oxidative stressinduced apoptosis by activation of SFKs. Exposure to oxidative stress such as UV irradiation induces the association of Ossa/C9orf10 with regulatory domains of SFKs, which activates these kinases and causes marked tyrosine phosphorylation of C9orf10 in turn. Tyrosine-phosphorylated Ossa recruits p85 subunits of phosphatidylinositol 3-kinase (PI3-kinase) and behaves as a scaffolding protein for PI3-kinase and SFKs, which activates the Akt-mediated antiapoptotic pathway. On the other hand, the carboxyl terminus of Ossa has a distinct function that directly binds RNAs such as insulin-like growth factor II (IGF-II) mRNA and promotes the extracellular secretion of IGF-II. Our findings indicate that Ossa is a dualfunctional protein and might be a novel therapeutic target which modulates the sensitivity of tumors to oxidative stress.

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Expression of insulin-like growth factor 2 mRNA in human gastric cancer.

Cited by 17 publications

References 0 publications

The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer.

The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer.

PTEN/MMAC1 enhances the growth inhibition by anticancer drugs with downregulation of IGF-II expression in gastric cancer cells

A Novel RNA-Binding Protein, Ossa/C9orf10, Regulates Activity of Src Kinases To Protect Cells from Oxidative Stress-Induced Apoptosis

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