Selective gene expression profiling of mTOR-associated tumor suppressor and oncogenes in ovarian cancer

Laudański, Piotr; Kowalczuk, Oksana; Klasa-Mazurkiewicz, Dagmara; Milczek, Tomasz; Rysak-Luberowicz, Dominik; Garbowicz, Magdalena; Baranowski, Włodzimierz; Charkiewicz, Radosław; Szamatowicz, Jacek; Chyczewski, L

doi:10.5603/fhc.2011.0044

Cited by 11 publications

(6 citation statements)

References 20 publications

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“…It has been demonstrated that PTEN and other autophagy-related genes are expressed in normal ovarian tissues, benign ovarian tumors and borderline ovarian tumors, but are downregulated in cases of ovarian cancer. This suggests that the decreased expression of autophagy-related proteins, such as PTEN, may be closely correlated with the development of ovarian cancer (19,20). In addition, PTEN protein expression has been identified to be positively correlated with the differentiation state of ovarian cancers (21).…”

Section: Discussionmentioning

confidence: 99%

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Ying

Liu

et al. 2015

Oncology Letters

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The aim of the present study was to investigate the protein expression of the autophagy-related genes, BECN1 and PTEN, and the association with drug resistance in epithelial ovarian cancers. In total, 40 patients with pathologically diagnosed epithelial ovarian cancer were divided into a chemotherapy-sensitive group (n=20) and a chemotherapy-resistant group (n=20), according to the results of the pre- or post-operative normative chemotherapy and the post-operative follow-up. The protein expression of the phosphatase and tensin homolog (PTEN) and the BECN1 gene product, Beclin-1, was analyzed using immunohistochemistry in the 40 patients with ovarian carcinoma. The positive rate of Beclin-1 expression was significantly lower in the resistant group (35.0%) compared with the sensitive group (50.0%). The positive rate of PTEN expression was also significantly lower in the resistant group (30.0%) compared with the sensitive group (65.0%). Furthermore, the differences in the expression rates were revealed to be significant (P<0.05). The expression of Beclin-1 was identified to be positively correlated with the expression of PTEN (rs=0.816; P<0.0001). The low expression of the Beclin-1 and PTEN proteins in the ovarian cancer tissues was revealed to be closely associated with drug resistance. Therefore, Beclin-1 may interact with PTEN to participate in the mechanism of drug resistance and the changes in macrophage activity observed in cases of drug-resistant ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Ying

Liu

et al. 2015

Oncology Letters

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“…Mutations in NF1 gene result in NF1 disease. Many studies have demonstrated that NF1 plays an important role in many cancers such as brain tumors [ 11 ], breast cancer [ 12 ], sporadic colon cancer [ 13 ], lung cancer [ 14 ], pheochromocytomas [ 15 ] and ovarian tumors [ 16 ]. Moreover, Vizcaino et al demonstrated that glioma patients with low NF1 expression were associated with poor overall survival and disease-specific survival [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Neurofibromatosis type-1 is a prognostic indicator in human gastric carcinoma

Liu

Zhang

et al. 2017

Oncotarget

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We investigated whether the Neurofibromatosis type-1(NF1) gene was of prognostic relevance to gastric cancer (GC) patients. Immunohistochemical staining of 160 matched GC tumor and adjacent normal tissue samples showed that 58.1% (93/160) of GC samples were NF1-positive as compared to 94.4% (151/160) of normal tissue samples (χ 2 =58.05, P <0.001). qRT-PCR analysis revealed that NF1 mRNA expression is lower in GC tissues than normal tissues (χ 2 =34.23, P <0.001). Moreover, NF1 protein and mRNA levels were associated with T stage (P <0.05) and TNM (P <0.001). No association was observed with other clinicopathological parameters, including gender, age, tumor size, lymph-node metastasis, cancer differentiation and distant metastasis (all P >0.05). Kaplan-Meier analysis revealed that negative or low NF1 were associated with poor overall survival (OS) in gastric cancer patients (P<0.001). Further univariate and multivariate cox regression analysis also showed that NF1 expression was an independent risk factor of survival of GC patients. These data show that NF1 has prognostic relevance to clinical outcomes in gastric cancer patients.

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“…In addition, the combination of K-Ras phosphorylation and PTEN deletion induced the phosphorylation of Akt, mTOR and p70S6 kinase indicating that the mTOR pathway, either by PI3 kinase/Akt or Ras/MAP kinase activation is involved in the transformation of endometriosis to ovarian cancer ( 30 ). This is further supported by the frequent downregulation of PTEN found in ovarian cancers ( 31 , 32 ) and increased K-Ras activation in endometriosis ( 33 , 34 ). In a more recent study using targeted next generation sequencing, it was shown that the PI3K-AKT-mTOR pathway may promote cell malignant transformation towards EAOC ( 35 ).…”

Section: Discussionmentioning

confidence: 67%

Differential expression of mTOR components in endometriosis and ovarian cancer: Effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry

et al. 2018

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Endometriosis is a well-known risk factor for ovarian cancer. The genetic changes that characterise endometriosis are poorly understood; however, the mechanistic target of rapamycin (mTOR) pathway is involved. In this study, we investigated the expression of key mTOR components in endometriosis and the effects of rapalogues using an endometrioid ovarian carcinoma cell line (MDAH 2774) as an in vitro model. Gene expression of mTOR, DEPTOR, Rictor and Raptor was assessed by qPCR in 24 endometriosis patients and in silico in ovarian cancer patients. Furthermore, the effects of Rapamycin, Everolimus, Deforolimus, Temsirolimus, Resveratrol, and BEZ235 (Dactolisib, a dual kinase inhibitor) on mTOR signalling components was assessed. mTOR showed a significant increase in the expression in endometriosis and ovarian endometrioid adenocarcinoma patients compared to non-affected controls. DEPTOR, an inhibitor of mTOR, was downregulated in the advanced stages of ovarian cancer (III and IV) compared to earlier stages (I and II). Treatment of MDAH-2774 cells with the mTOR inhibitors resulted in the significant upregulation of DEPTOR mRNA, whereas treatment with rapamycin and BEZ-235 (100 nM) resulted in downregulation of the mTOR protein expression after 48 h of treatment. None of the treatments resulted in translocation of mTOR from cytoplasm to nucleus. Upregulation of DEPTOR is a positive prognostic marker in ovarian cancer and is increased in response to mTOR pathway inhibition suggesting that it functions as a tumour suppressor gene in endometrioid ovarian carcinoma. Collectively, our data suggest the mTOR pathway as a potential connection between endometriosis and ovarian cancer and may be a potential target in the treatment of both conditions.

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Selective gene expression profiling of mTOR-associated tumor suppressor and oncogenes in ovarian cancer

Cited by 11 publications

References 20 publications

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Neurofibromatosis type-1 is a prognostic indicator in human gastric carcinoma

Differential expression of mTOR components in endometriosis and ovarian cancer: Effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry

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