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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00235

Differentially expressed genes and molecular pathways in an autochthonous mouse prostate cancer model

Shiv Verma1, Sanjeev Shukla1, Mitali Pandey2, Gregory T. MacLennan1 and  Sanjay Gupta3*
  • 1School of Medicine, Case Western Reserve University, United States
  • 2The Vancouver Prostate Centre, Canada
  • 3Urology, Case Western Reserve University, United States

Prostate cancer remains a major public health problem and the second leading cause of cancer-related deaths in men in the United States. The present study aims to understand the molecular pathway(s) of prostate cancer which is essential for early detection and treatment. Dorsolateral prostate from 20 week transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which spontaneously develops prostate cancer and recapitulates human disease and age-matched non-transgenic littermates were utilized for microarray analysis. Mouse genome network and pathway analyses were mapped to the human genome using the Ingenuity Pathway Analysis (IPA) database for annotation, visualization and integrated discovery. In total, 136 differentially expressed genes, including 32 downregulated genes and 104 upregulated genes were identified in the dorsolateral prostate of TRAMP, compared to non-transgenic mice. A subset of differentially expressed genes were validated by qRT-PCR. Alignment with human genome database identified 18 different classes of proteins, among these, 36% were connected to the nucleic acid binding, including ribosomal proteins, which play important role in protein synthesis – the most enriched pathway in the development of prostate cancer. Furthermore, the results suggest deregulation of signaling molecules (9%) and enzyme modulators (8%) affect various pathways. An imbalance in other protein classes, including transporter proteins (7%), hydrolases (6%), oxidoreductases and cytoskeleton proteins (5%), contribute to cancer progression. Our study evaluated the underlying pathways and its connection to human prostate cancer, which may further help assess the risk of disease development and progression and identify potential targets for therapeutic intervention.

Keywords: biomarkers, Therapeutic target, prostate cancer, Gene Expression, TRAMP mice

Received: 26 Oct 2018; Accepted: 04 Mar 2019.

Edited by:

Alessandro Laganà, Icahn School of Medicine at Mount Sinai, United States

Reviewed by:

Matteo D'Antonio, University of California, San Diego, United States
Andrew Dellinger, Elon University, United States  

Copyright: © 2019 Verma, Shukla, Pandey, MacLennan and Gupta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Sanjay Gupta, Case Western Reserve University, Urology, Cleveland, 44106, Ohio, United States, sanjay.gupta@case.edu