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The Gene Expression Status of the PI3K/AKT/mTOR Pathway in Gastric Cancer Tissues and Cell Lines

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Pathology & Oncology Research

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.

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Acknowledgments

The authors would like to thank to Judy Romero-Gallo from Vanderbilt University Medical Center (Nashville, Tennessee, USA) for their invaluable help in the performance of this work. This study was supported by the Chilean National Fund for Scientific and Technological Development (FONDECYT NO. 1090171 and FONDECYT No. 1130204), the Chilean National Commission for Scientific and Technological Research (CONICYT) through the PhD scholarship and financial support for doctoral thesis NO. 24121456 and the Grant CONICYT-FONDAP No. 15130011. Ismael Riquelme also thanks to the Postdoctoral Scholarship from the Universidad de La Frontera.

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Authors and Affiliations

  1. Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Avenida Alemania 0458, Postal Code, 4810296, Temuco, Chile

    Ismael Riquelme, Oscar Tapia & Kurt Buchegger

  2. Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Avenida Francisco Salazar 01145,Casilla 54-D, Temuco, Chile

    Ismael Riquelme & Kurt Buchegger

  3. Department of Pathology, Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile

    Jaime A. Espinoza, Carolina Bizama & Juan Carlos Roa

  4. UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Portugal 61, Postal Code, 8330034, Santiago, Chile

    Jaime A. Espinoza, Alejandra Sandoval, Carolina Bizama & Juan Carlos Roa

  5. Advanced Centre for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Marcoleta 377, 7th Floor, Postal Code, 8330024, Santiago, Chile

    Jaime A. Espinoza, Alejandra Sandoval, Carolina Bizama & Juan Carlos Roa

  6. Molecular Biology and Biomedicine Lab, CEGIN-BIOREN, Universidad de La Frontera, Avenida Alemania 0458, Postal Code, 4810296, Temuco, Chile

    Pamela Leal

  7. Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Avenida Alemania 0458, Postal Code, 4810296, Temuco, Chile

    Juan Carlos Araya

  8. Division of Gastroenterology, Department of Medicine and Cancer Biology, School of Medicine, Vanderbilt University, 2215 Garland Avenue Nashville, Postal Code, Nashville, TN, 37232, USA

    Richard M. Peek

Authors
  1. Ismael Riquelme
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  2. Oscar Tapia
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  3. Jaime A. Espinoza
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  4. Pamela Leal
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  5. Kurt Buchegger
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  6. Alejandra Sandoval
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  7. Carolina Bizama
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  8. Juan Carlos Araya
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  9. Richard M. Peek
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  10. Juan Carlos Roa
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Corresponding author

Correspondence to Juan Carlos Roa.

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Authors report no conflicts of interest.

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Ismael Riquelme & Oscar Tapia contributed equally to this work.

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Riquelme, I., Tapia, O., Espinoza, J.A. et al. The Gene Expression Status of the PI3K/AKT/mTOR Pathway in Gastric Cancer Tissues and Cell Lines. Pathol. Oncol. Res. 22, 797–805 (2016). https://doi.org/10.1007/s12253-016-0066-5

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  • DOI: https://doi.org/10.1007/s12253-016-0066-5

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