Significance of Akt Phosphorylation on Tumor Growth and Vascular Endothelial Growth Factor Expression in Human Gastric Carcinoma

Kobayashi, Iwao; Semba, Shuho; Matsuda, Yoshiko; Kuroda, Yoshikazu; Yokozaki, Hiroshi

doi:10.1159/000093087

Cited by 51 publications

(45 citation statements)

References 56 publications

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“…Our data are in agreement with a previous study, reporting that Akt activation is related to a poor outcome in gastric cancer [41]. We also analyzed the relationship between pAkt expression and apoptotic index, because Akt has been reported to be a signal transduction protein capable of controlling the balance between cell survival and apoptosis [5,45]. It is known that phosphorylation of Akt is promoted by phosphatidylinositides converted by PI3K products at the cytoplasmatic level.…”

Section: Discussionsupporting

confidence: 91%

Activated Akt as an indicator of prognosis in gastric cancer

Cinti

Vindigni

Zamparelli³

et al. 2008

Virchows Arch

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The immunohistochemical expression of phosphorylated (activated) Akt (pAkt) in 50 advanced gastric carcinomas has been analyzed and the results correlated with age, sex, location in the stomach, histotype, stage, survival, mitotic and apoptotic index, some cell cycle regulators (cyclin D1, cyclin E, p34/cdc2, p27/kip1), and cell proliferation. There was a statistically significant direct correlation between pAkt expression (both cytoplasmatic and nuclear) and depth of infiltration of the tumor, number of infiltrated lymph nodes and p34/cdc2 expression, and between prevalently nuclear pAkt and cyclin D1 and cyclin E. Conversely, there was a significant inverse correlation between nuclear pAkt and apoptotic index and between cytoplasmatic and nuclear pAkt and patient survival. No correlation was found between pAkt and sex, age, tumor location, histotype, mitotic index, and cell proliferation. These findings suggest that pAkt may be considered an indicator of tumor progression and patient survival in gastric cancer.

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Section: Discussionsupporting

confidence: 91%

Activated Akt as an indicator of prognosis in gastric cancer

Cinti

Vindigni

Zamparelli³

et al. 2008

Virchows Arch

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“…The activation of the PI3K/AKT signaling pathway has been reported in several malignancies such as breast [32], lung [33], and head and neck carcinomas [34]. In gastric cancer, a previous study showed that the IHC expression of p-AKT was correlated with clinicopathological features such as vessel infiltration and lymph node metastasis [35]. Our study revealed that LOH of PTEN causes an activation of the PI3K/AKT signaling pathway, leading to an adverse outcome in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Loss of Heterozygosity of PTEN (Encoding Phosphate and Tensin Homolog) Associated with Elevated HER2 Expression Is an Adverse Prognostic Indicator in Gastric Cancer

Zaitsu¹,

Oki²,

Ando³

et al. 2014

Oncology

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Objective: PTEN (the encoding phosphate and tensin homolog) is a well-known cancer suppressor gene and its mutation and loss of heterozygosity (LOH) occurs in various types of carcinomas. This study aimed to examine the association between LOH of PTEN and prognosis in HER2-expressing and nonexpressing gastric cancer patients. Methods: Fresh-frozen tumor samples of 221 gastric cancer patients with a primary diagnosis of gastric carcinoma were examined for LOH of PTEN. The results were compared with pathological parameters and the HER2 status. To elucidate the role of LOH of PTEN, the activation of the PI3K/AKT pathway was examined immunohistochemically using a phosphorylation-specific antibody. Results: LOH of PTEN was observed in 20% of the patients (39 of 195 cases). LOH of PTEN was associated with vascular involvement (25 of 39 cases; p = 0.0083), equivocal to positive staining for HER2 (p = 0.0080), and phospho-Akt expression (p = 0.0067). Patients with HER2-expressing gastric cancer with LOH of PTEN had a significantly worse prognosis (p = 0.0050). Conclusions: Although HER2 expression itself was not a prognostic factor, the combination of HER2 expression and LOH of PTEN exacerbates the malignant potential of gastric cancer through its proliferative function. © 2014 S. Karger AG, Basel

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“…The serine/threonine kinase Akt plays an essential role in various cellular processes, including cell growth and proliferation, metabolism and cell survival. Immunohistochemical analyses have shown that Akt is activated in many types of carcinoma and preneoplastic lesions, and Akt activation is associated with tumor progression and poor prognosis in various human malignancies [23][24][25][26][27] . However, in NSCLCs, the results so far are conflicting.…”

Section: Discussionmentioning

confidence: 99%

Expression of the Mammalian Target of Rapamycin Pathway Markers in Lung Adenocarcinoma and Squamous Cell Carcinoma

Kim

Lim

et al. 2012

Pathobiology

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Objective: We investigated whether the expression of mammalian target of rapamycin (mTOR) pathway components is associated with clinicopathologic characteristics and patient outcome in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). Methods: We used immunohistochemistry to evaluate the expression of phosphorylated Akt (pAkt), mTOR, p70 ribosomal protein S6 kinase (p70S6K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in 91 cases of AC and 154 cases of SCC. Results: pAkt expression was positively correlated with the expression of mTOR (p < 0.001) and p70S6K (p < 0.001), and mTOR expression was positively correlated with p70S6K expression (p < 0.001). PTEN expression was inversely correlated with the expression of pAkt (p = 0.001), mTOR (p < 0.001) and p70S6K (p = 0.012). In addition, loss of PTEN expression, observed in 37.4% (34/91) of AC patients, was significantly associated with a higher histologic grade (p = 0.013), pathologic T stage (p = 0.016) and N stage (p < 0.001) and advanced TNM stage (p = 0.001), as well as a shorter overall survival of AC patients (p = 0.015). Conclusion: The high prevalence of PTEN loss and its association with aggressive tumor behavior and poor patient outcome in AC suggest that loss of PTEN expression is involved in AC progression and serves as a prognostic marker for patients with AC.

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Significance of Akt Phosphorylation on Tumor Growth and Vascular Endothelial Growth Factor Expression in Human Gastric Carcinoma

Cited by 51 publications

References 56 publications

Activated Akt as an indicator of prognosis in gastric cancer

Activated Akt as an indicator of prognosis in gastric cancer

Loss of Heterozygosity of PTEN (Encoding Phosphate and Tensin Homolog) Associated with Elevated HER2 Expression Is an Adverse Prognostic Indicator in Gastric Cancer

Expression of the Mammalian Target of Rapamycin Pathway Markers in Lung Adenocarcinoma and Squamous Cell Carcinoma

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