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 M Smith, Sonny Johansson, Subodh M Lele, Michel M Ouellette, Moorthy Palanimuthu Ponnusamy, Surinder Kumar Batra

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3317-3331
Number of pages15
JournalOncotarget
Volume7
Issue number3
DOIs
StatePublished - Jan 1 2016

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Adenocarcinoma
Neoplasm Metastasis
Carcinogenesis
Up-Regulation
Cyclin D1
Oncogenes
Neoplastic Stem Cells
Pancreatic Ducts
Telomerase
Pancreas
Cell Cycle
Growth
Neoplasms
Therapeutics

Keywords

  • C-Myc
  • CSC
  • PD2
  • PDAC

ASJC Scopus subject areas

  • Oncology

Cite this

Overexpression of PD2 leads to increased tumorigenicity and metastasis in pancreatic ductal adenocarcinoma. / Vaz, Arokia Priyanka; Deb, Shonali; Rachagani, Satyanarayana; Dey, Parama; Muniyan, Sakthivel; Lakshmanan, Imayavaramban; Karmakar, Saswati; Smith, Lynette M; Johansson, Sonny; Lele, Subodh M; Ouellette, Michel M; Palanimuthu Ponnusamy, Moorthy; Batra, Surinder Kumar.

In: Oncotarget, Vol. 7, No. 3, 01.01.2016, p. 3317-3331.

Research output: Contribution to journalArticle

Vaz, Arokia Priyanka ; Deb, Shonali ; Rachagani, Satyanarayana ; Dey, Parama ; Muniyan, Sakthivel ; Lakshmanan, Imayavaramban ; Karmakar, Saswati ; Smith, Lynette M ; Johansson, Sonny ; Lele, Subodh M ; Ouellette, Michel M ; Palanimuthu Ponnusamy, Moorthy ; Batra, Surinder Kumar. / Overexpression of PD2 leads to increased tumorigenicity and metastasis in pancreatic ductal adenocarcinoma. In: Oncotarget. 2016 ; Vol. 7, No. 3. pp. 3317-3331.
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AU - Vaz, Arokia Priyanka

AU - Deb, Shonali

AU - Rachagani, Satyanarayana

AU - Dey, Parama

AU - Muniyan, Sakthivel

AU - Lakshmanan, Imayavaramban

AU - Karmakar, Saswati

AU - Smith, Lynette M

AU - Johansson, Sonny

AU - Lele, Subodh M

AU - Ouellette, Michel M

AU - Palanimuthu Ponnusamy, Moorthy

AU - Batra, Surinder Kumar

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