CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis

Ann Surg Oncol. 2011 Mar;18(3):857-65. doi: 10.1245/s10434-010-1313-8. Epub 2010 Sep 15.

Abstract

Background: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein inhibiting proteolytic degradation of c-MYC. In this study, we investigated the clinical relevance of CIP2A in NSCLC.

Materials and methods: We analyzed CIP2A mRNA expression in 29 NSCLC tissues using quantitative reverse transcription polymerase chain reaction (RT-QPCR). We also examined the expression of CIP2A protein by immunohistochemistry in 90 lung cancer specimens and correlated its expression with c-MYC expression and clinicopathological parameters. The functional roles of CIP2A in lung cancer cell lines were evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion.

Results: In 29 lung cancer tissues examined, 24 of them (82.7%) exhibited much stronger levels of CIP2A mRNA compared with their corresponding normal tissues. Moreover, CIP2A mRNA expression levels correlated with c-MYC mRNA levels. Furthermore, CIP2A protein was found to be overexpressed in 72.2% of 90 human lung cancer samples and correlated with poor survival (P < 0.05). In addition, the CIP2A status was a significant prognostic factor for NSCLC patients (P = 0.0136). Depleting CIP2A expression inhibited growth and clonogenic potential in lung cancer cell lines.

Conclusions: CIP2A is an oncoprotein overexpressed in NSCLC, and its expression is associated with poor prognosis and malignant cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Autoantigens / genetics*
  • Autoantigens / metabolism
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Intracellular Signaling Peptides and Proteins
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Autoantigens
  • CIP2A protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA, Small Interfering