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

Hwang, Pyoung Han; Kim, Sun Young; Lee, Jung Chang; Kim, Sun Jun; Yi, Ho Keun; Lee, Dae Yeol

doi:10.1038/emm.2005.49

Cited by 18 publications

(12 citation statements)

References 27 publications

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“…IGF2 encodes insulin-like growth factor-II (IGF-II); a peptide growth factor with structural and functional similarities to insulin. In contrast to its well-established roles in promoting cancer growth [30][31][32][33], relatively little is known about the roles of IGF-II in benign broproliferative diseases like FFS and DD. In addition to DD [18], IGF2 expression and IGF-II levels are reported to be increased in systemic sclerosisassociated pulmonary brosis [34].…”

mentioning

confidence: 99%

IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome

Raykha¹,

Crawford²,

Burry³

et al. 2014

CIM

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IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome Abstract Purpose: Frozen Shoulder Syndrome is a brosis of the shoulder joint capsule that is clinically associated with Dupuytren's disease, a brosis of the palmar fascia. Little is known about any commonalities in the pathophysiology of these connective tissue broses. β-catenin, a protein that transactivates gene expression, and levels of IGF2 mRNA, encoding insulin-like growth factor-II, are elevated in Dupuytren's disease. e aim of this study was to determine if correlating changes in β-catenin levels and IGF2 expression are evident in Frozen Shoulder Syndrome.Methods: Tissue from patients with Frozen Shoulder Syndrome and rotator cu tear were obtained during shoulder arthroscopies. Total protein extracts were prepared from tissue aliquots and β-catenin immunoreactivity was assessed by Western immunoblotting. In parallel, primary broblasts were derived from these tissues and assessed for IGF2 expression by quantitative PCR.Results: β-catenin levels were signi cantly increased in Frozen Shoulder Syndrome relative to rotator cu tear when assessed by Western immunoblotting analyses. IGF2 mRNA levels were signi cantly increased in primary broblasts derived from frozen shoulder syndrome tissues relative to broblasts derived from rotator cu tissues. Conclusions:As in Dupuytren's disease, β-catenin levels and IGF2 expression are elevated in Frozen Shoulder Syndrome. ese ndings support the hypothesis that these connective tissue broses share a common pathophysiology. Materials and Methods Tissue collectionTissue sections were collected with approval of the Human Subjects Research Ethics Board (HSREB) at Western University from surgical specimens of patients undergoing shoulder arthroscopy for the treatment of either FSS or subacromial decompression for RCT. An arthroscopic punch was used to obtain tissue specimens from the rotator cu interval immediately adjacent to the antero-superior arthroscopic portal from patients with FSS and RCT. Representative samples of these tissues were removed at the time of surgery and immediately transported to the laboratory. e tissues were either snap frozen in liquid nitrogen for total protein extraction or processed for primary broblast derivation. Western immunoblottingTotal protein extracts were prepared from snap frozen tissue using modi ed RIPA bu er. Tissue lysate (25 μg) was subjected to Western blot analysis and β-catenin levels were assessed using an anti-β-catenin monoclonal antibody (clone 14, Transduction Laboratories, Lexington, KY). β-actin levels were assessed in parallel using an anti-β-actin antibody (Sigma, St Louis, MO) to normalize for variability in total protein loading. Antibody speci c bands were visualized using enhanced chemiluminescence (ECL) and Kodak XLS lm. Densitometry analysis was carried out using Scion Image so ware (Scion Corporation, Beta 4.0.2, Frederick, MD). Normalized measurements of β-catenin were plotted as the sample mean (β-catenin /actin) ratio ± standard error...

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confidence: 99%

IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome

Raykha¹,

Crawford²,

Burry³

et al. 2014

CIM

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“…Furthermore, the mutation rate was higher in poorly differentiated gastric cancer than in well and moderately differentiated pathological types (P<0.05). These results suggest that PTEN may play an important role in regulation of infiltration and metastasis of gastric cancer, and PTEN gene might be a prognostic biomarker of gastric cancer (5,33,34).…”

Section: Discussionmentioning

confidence: 73%

Mutation analysis of tumor suppressor gene PTEN in patients with gastric carcinomas and its impact on PI3K/AKT pathway

Tang¹

2010

Oncol Rep

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Abstract. The aim of this study was to clarify the participation of PTEN mutation in gastric carcinogenesis and its impact on PI3K/AKT pathway. All nine exons of PTEN were screened for mutations by direct sequencing in 144 patients with pathologically proven gastric carcinoma and their corresponding normal mucosae, followed by Western blotting to detect the changes in PI3K/AKT pathway. Direct sequencing indicated there were 27 cases with mutations among 144 patients consisting of 15 cases (55.6%) of missense mutation, nine nonsense mutations (33.3%), two 1-bp deletion (7.4%), and a mutation within intron 6 (3.7%). The mutation hot spots at codons 36, 75, 232 and 393 had not been observed previously, and the mutation sites in exons 3, 5, 6 and 8 were not found, suggesting that there might be some unique characteristic of PTEN inactivation mechanism in the Shanghai population. The PTEN mutation rate was significantly higher at pTMN stages III and IV than that at stages I and II (P<0.005), and it was higher in poorly differentiated gastric cancer than in well or moderately differentiated types (P<0.05). PTEN and E-cadherin protein expression in gastric cancer was significantly down-regulated comparing with that in paracancerous tissues, while the PI3K, AKT, MMP-2, MMP-9 and NF-κBp65 protein were overexpressed in cancer tissues. Our results implicated that the mutations of PTEN did not occur at a significant rate in gastric carcinoma in Shanghai, but might play a role in tumorigenesis. The mutation status of PTEN was significantly relevant to pTNM staging and degree of cell differentiation, hinting that PTEN might be a prognostic biomarker of gastric cancer. The decreased expression of PTEN and E-cadherin, together with the overexpression of PI3K, AKT, MMP-2, MMP-9 and NF-κBp65, contributed cooperatively to the accelerated progress of gastric cancer.

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“…Concomitantly, they also detected a reduction in VEGF and MMP-9 concentration in the culture supernatant, and inferred that exogenous PTEN may inhibit the growth and proliferation of SGC7901 cells by suppressing the expression of VEGF and MMP-9. In other studies, Hwang et al (Hwang et al, 2005) and Hang et al (Hang et al, 2005) found that exogenous PTEN significantly suppressed proliferation, and induced apoptosis and cell cycle arrest in gastric cancer cells. Hang et al also demonstrated that exogenous PTEN could inhibit Akt, FAK and p44/42 MAPK pathway in gastric cancer cells, but had no effect on normal cells, suggesting that PTEN may have a selective apoptotic effect on tumor cells.…”

Section: Pten Inactivation and Chemoresistancementioning

confidence: 89%

“…Oki et al (Oki et al, 2005) found that gastric cancer patients who carry a loss of heterozygosity in PTEN are less sensitive to chemotherapy. Hwang et al (Hwang et al, 2005) demonstrated that overexpression of PTEN in SNU-5 or SNU-216 gastric cancer cell lines could increase apoptosis induced by etoposide or doxorubicin. In a study by Yu et al (Yu et al, 2008), overexpression of PTEN in transfected human gastric cancer cell line BGC-823, was shown to reduce the basal and post-chemotherapy activity of Akt kinases while increasing cell sensitivity to etoposide or doxorubicin.…”

Section: Pten Inactivation and Chemoresistancementioning

confidence: 99%