Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells. Academic Article uri icon

Overview

abstract

  • PURPOSE: The targeting protein for Xklp2 (TPX2) has recently gained attention as a putative oncogene possibly amplified in several human malignancies, including pancreatic adenocarcinoma. In this work, we sought to evaluate the copy number and expression of TPX2 in pancreatic cancer cell lines and tumor tissues and to further explore the potential of TPX2 as a therapeutic target. EXPERIMENTAL DESIGN: The DNA copy number and expression of the TPX2 gene were surveyed in pancreatic cancer cell lines and tumor tissues and compared with those of immortalized normal pancreatic ductal cells and normal pancreatic tissues. The cellular effects of TPX2 knockdown using small interfering RNA oligonucleotides in pancreatic cancer cells, such as growth in tissue culture, in soft agar, and in nude mice; apoptosis; and sensitivity to paclitaxel, were also investigated using various assays. RESULTS: Low-copy-number TPX2 amplification was found in pancreatic cancer cell lines and low-passage pancreatic cancer tumor xenografts. TPX2 expression was upregulated in pancreatic cancer cell lines at both the mRNA and protein levels relative to the immortalized pancreatic ductal epithelial cell line HPDE6. Immunohistochemical staining of a tissue microarray showed that TPX2 expression was higher in pancreatic tumors compared with their normal counterparts. Treatment with TPX2 targeting small interfering RNAs effectively reduced pancreatic cancer cell growth in tissue culture, induced apoptosis, and inhibited growth in soft agar and in nude mice. Knockdown of TPX2 also sensitized pancreatic cancer cells to paclitaxel treatment. CONCLUSIONS: Our results suggest that TPX2 might be an attractive target for pancreatic cancer therapy.

publication date

  • October 27, 2009

Research

keywords

  • Adenocarcinoma
  • Cell Cycle Proteins
  • Drug Delivery Systems
  • Gene Dosage
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Pancreatic Neoplasms
  • Up-Regulation

Identity

PubMed Central ID

  • PMC2783218

Scopus Document Identifier

  • 70350743121

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-09-0077

PubMed ID

  • 19861455

Additional Document Info

volume

  • 15

issue

  • 21