title: The Gene Expression Status of the PI3K/AKT/mTOR Pathway in Gastric Cancer Tissues and Cell Lines.
abstract: The PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism and angiogenesis. Emerging evidence has shown that deregulation of this pathway has a role promoting gastric cancer (GC). The aim was to assess the expression of genes involved in this pathway by qPCR in 23 tumor and 23 non-tumor gastric mucosa samples from advanced GC patients, and in AGS, MKN28 and MKN45 gastric cancer cell lines. Results showed a slight overexpression of PIK3CA, PIK3CB, AKT1, MTOR, RPS6KB1, EIF4EBP1 and EIF4E genes, and a slightly decreased PTEN and TSC1 expression. In AGS, MKN28 and MKN45 cells a significant gene overexpression of PIK3CA, PIK3CB, AKT1, MTOR, RPS6KB1 and EIF4E, and a significant repression of PTEN gene expression were observed. Immunoblotting showed that PI3K-β, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E and p-eIF4E proteins were present in cell lines at different levels, confirming activation of this pathway in vitro. This is the first time this extensive panel of 9 genes within PI3K/AKT/mTOR pathway has been studied in GC to clarify the biological role of this pathway in GC and develop new strategies for this malignancy.
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Avenida Alemania 0458, Postal Code, 4810296, Temuco, Chile.|Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Avenida Francisco Salazar 01145,Casilla 54-D, Temuco, Chile.
authors.forename: Ismael
authors.initials: I
authors.lastname: Riquelme
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Avenida Alemania 0458, Postal Code, 4810296, Temuco, Chile.
authors.forename: Oscar
authors.initials: O
authors.lastname: Tapia
authors.affiliation: Department of Pathology, Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile.|UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Portugal 61, Postal Code, 8330034, Santiago, Chile.|Advanced Centre for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile.
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Espinoza
authors.affiliation: Molecular Biology and Biomedicine Lab, CEGIN-BIOREN, Universidad de La Frontera, Avenida Alemania 0458, Postal Code, 4810296, Temuco, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Leal
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Avenida Alemania 0458, Postal Code, 4810296, Temuco, Chile.|Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Avenida Francisco Salazar 01145,Casilla 54-D, Temuco, Chile.
authors.forename: Kurt
authors.initials: K
authors.lastname: Buchegger
authors.affiliation: UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Portugal 61, Postal Code, 8330034, Santiago, Chile.|Advanced Centre for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Sandoval
authors.affiliation: Department of Pathology, Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile.|UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Portugal 61, Postal Code, 8330034, Santiago, Chile.|Advanced Centre for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Bizama
authors.affiliation: Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Avenida Alemania 0458, Postal Code, 4810296, Temuco, Chile.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Araya
authors.affiliation: Division of Gastroenterology, Department of Medicine and Cancer Biology, School of Medicine, Vanderbilt University, 2215 Garland Avenue Nashville, Postal Code, Nashville, TN, 37232, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.affiliation: Department of Pathology, Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile. jcroa@med.puc.cl.|UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Portugal 61, Postal Code, 8330034, Santiago, Chile. jcroa@med.puc.cl.|Advanced Centre for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile. jcroa@med.puc.cl.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Roa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C087000:EIF4EBP1 protein, human; C546842:MTOR protein, human; C484760:PIK3CA protein, human; C494929:PTEN protein, human
keywords: AGS, MKN28 and MKN45 cell lines; Gastric cancer; PI3K/AKT/mTOR pathway