Down-regulation of yes associated protein 1 expression reduces cell proliferation and clonogenicity of pancreatic cancer cells

Caroline H. Diep, Kelly M. Zucker, Galen Hostetter, Aprill Watanabe, Chengcheng Hu, Ruben M. Munoz, Daniel D. von Hoff, Haiyong Han

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: The Hippo pathway regulates organ size by inhibiting cell proliferation and promoting cell apoptosis upon its activation. The Yes Associated Protein 1 (YAP1) is a nuclear effector of the Hippo pathway that promotes cell growth as a transcription co-activator. In human cancer, the YAP1 gene was reported as amplified and over-expressed in several tumor types. Methods: Immunohistochemical staining of YAP1 protein was used to assess the expression of YAP1 in pancreatic tumor tissues. siRNA oligonucleotides were used to knockdown the expression of YAP1 and their effects on pancreatic cancer cells were investigated using cell proliferation, apoptosis, and anchorage-independent growth assays. The Wilcoxon signed-rank, Pearson correlation coefficient, Kendall's Tau, Spearman's Rho, and an independent two-sample t (two-tailed) test were used to determine the statistical significance of the data. Results: Immunohistochemistry studies in pancreatic tumor tissues revealed YAP1 staining intensities were moderate to strong in the nucleus and cytoplasm of the tumor cells, whereas the adjacent normal epithelial showed negative to weak staining. In cultured cells, YAP1 expression and localization was modulated by cell density. YAP1 total protein expression increased in the nuclear fractions in BxPC-3 and PANC-1, while it declined in HPDE6 as cell density increased. Additionally, treatment of pancreatic cancer cell lines, BxPC-3 and PANC-1, with YAP1-targeting siRNA oligonucleotides significantly reduced their proliferation in vitro. Furthermore, treatment with YAP1 siRNA oligonucleotides diminished the anchorage-independent growth on soft agar of pancreatic cancer cells, suggesting a role of YAP1 in pancreatic cancer tumorigenesis. Conclusions: YAP1 is overexpressed in pancreatic cancer tissues and potentially plays an important role in the clonogenicity and growth of pancreatic cancer cells.

Original languageEnglish (US)
Article numbere32783
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2012

Fingerprint

pancreatic neoplasms
Cell proliferation
Pancreatic Neoplasms
cell proliferation
Down-Regulation
Cells
Cell Proliferation
Proteins
proteins
Tumors
small interfering RNA
oligonucleotides
Oligonucleotides
Small Interfering RNA
neoplasms
Neoplasms
Staining and Labeling
Growth
Tissue
neoplasm cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Down-regulation of yes associated protein 1 expression reduces cell proliferation and clonogenicity of pancreatic cancer cells. / Diep, Caroline H.; Zucker, Kelly M.; Hostetter, Galen; Watanabe, Aprill; Hu, Chengcheng; Munoz, Ruben M.; von Hoff, Daniel D.; Han, Haiyong.

In: PLoS One, Vol. 7, No. 3, e32783, 01.03.2012.

Research output: Contribution to journalArticle

Diep, Caroline H. ; Zucker, Kelly M. ; Hostetter, Galen ; Watanabe, Aprill ; Hu, Chengcheng ; Munoz, Ruben M. ; von Hoff, Daniel D. ; Han, Haiyong. / Down-regulation of yes associated protein 1 expression reduces cell proliferation and clonogenicity of pancreatic cancer cells. In: PLoS One. 2012 ; Vol. 7, No. 3.
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