WWOX gene restoration prevents lung cancer growth in vitro and in vitro

Muller Fabbri, Dimitrios Iliopoulos, Francesco Trapasso, Rami I. Aqeilan, Amelia Cimmino, Nicola Zanesi, Sai Yendamuri, Shuang Yin Han, Dino Amadori, Kay Huebner, Carlo M. Croce

Research output: Contribution to journalArticle

Abstract

The WWOX (WW domain containing oxidoreductase) gene at the common fragile site, FRA16D, is altered in many types of cancer, including lung cancer. We have examined the tumor suppressor function of WWOX in preclinical lung cancer models. The WWOX gene was expressed in lung cancer cell lines through recombinant adenovirus (Ad) infection (Ad-WWOX), and through a drug [ponasterone A, (ponA)]-inducible system. After WWOX restoration in vitro, endogenous Wwox protein-negative cell lines (A549, H460, and H1299) underwent apoptosis through activation of the intrinsic apoptotic caspase cascade in A549 and H460 cells. Ectopic expression of Wwox caused dramatic suppression of tumorigenicity of A549, H460, and H1299 cells in nude mice after Ad-WWOX infection and after ponA induction of Wwox expression in H1299 lung cancer cells. Tumorigenicity and in vitro growth of U2020 (Wwox-positive) lung cancer cells was unaffected by Wwox overexpression. This study confirms that WWOX is a tumor suppressor gene and is highly effective in preventing growth of lung cancer xenografts, whether introduced through viral infection or by induction of a silent WWOX transgene.

Original languageEnglish
Pages (from-to)15611-15616
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number43
DOIs
Publication statusPublished - Oct 25 2005

Keywords

  • Adenovirus
  • Inducible expression
  • Viral gene transduction

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'WWOX gene restoration prevents lung cancer growth in vitro and in vitro'. Together they form a unique fingerprint.

  • Cite this

    Fabbri, M., Iliopoulos, D., Trapasso, F., Aqeilan, R. I., Cimmino, A., Zanesi, N., Yendamuri, S., Han, S. Y., Amadori, D., Huebner, K., & Croce, C. M. (2005). WWOX gene restoration prevents lung cancer growth in vitro and in vitro. Proceedings of the National Academy of Sciences of the United States of America, 102(43), 15611-15616. https://doi.org/10.1073/pnas.0505485102