Research Papers:

Overexpression of PD2 leads to increased tumorigenicity and metastasis in pancreatic ductal adenocarcinoma

Arokia Priyanka Vaz, Shonali Deb, Satyanarayana Rachagani, Parama Dey, Sakthivel Muniyan, Imayavaramban Lakshmanan, Saswati Karmakar, Lynette Smith, Sonny Johansson, Subodh Lele, Michel Ouellette, Moorthy P. Ponnusamy and Surinder K. Batra _

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Oncotarget. 2016; 7:3317-3331. https://doi.org/10.18632/oncotarget.6580

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Arokia Priyanka Vaz1, Shonali Deb1, Satyanarayana Rachagani1, Parama Dey1, Sakthivel Muniyan1, Imayavaramban Lakshmanan1, Saswati Karmakar1, Lynette Smith2, Sonny Johansson3, Subodh Lele3, Michel Ouellette1,4, Moorthy P. Ponnusamy1,5, Surinder K. Batra1,3,5

1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

2Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA

3Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

4Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE, USA

5Eppley Institute for Research in Cancer and Allied Disease, University of Nebraska Medical Center, Omaha, NE, USA

Correspondence to:

Surinder K. Batra, e-mail: [email protected]

Moorthy P. Ponnusamy, e-mail: [email protected]

Keywords: PD2, CSC, c-Myc, PDAC

Received: August 12, 2015     Accepted: November 16, 2015     Published: December 12, 2015


Pancreatic differentiation 2 (PD2), an important subunit of the human PAF complex, was identified after differential screening analysis of 19q13 amplicon, and its overexpression induces oncogenic transformation of NIH3T3 cells, hence raising the possibility of a role for PD2 in tumorigenesis and metastasis. To test this hypothesis, we analyzed here the functional role and clinical significance of PD2 in pancreatic ductal adenocarcinoma (PDAC) and its pathogenesis. Using immunohistochemical analysis, we found that PD2 is detected in the acini but not in the ducts in the normal pancreas. In human PDAC specimens, PD2 was instead primarily detected in the ducts (12/48 patients 25%; p-value < 0.0001), thereby showing that PDAC correlates with increased ductal expression of PD2. Consistently, PD2 expression was increased in telomerase-immortalized human pancreatic ductal cells (HPNE cells) modified to express the HPV16 E6 and E7 proteins, whose respective functions are to block p53 and RB. In addition, ectopic expression of PD2 in PDAC cells (Capan-1 and SW1990) led to increased clonogenicity and migration in vitro, and tumor growth and metastasis in vivo. Interestingly, PD2 overexpression also resulted in enrichment of cancer stem cells (CSCs) and upregulation of oncogenes such as c-Myc and cell cycle progression marker, cyclin D1. Taken together, our results support that PD2 is overexpressed in the ducts of PDAC tissues, and results in tumorigenesis and metastasis via upregulation of oncogenes such as c-Myc and cyclin hence D1 implicating PD2 upregulation in pancreatic oncogenesis with targeted therapeutic potential.

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