Alterations of the Tumor Suppressor Gene Parkin in Non-Small Cell Lung Cancer

Maria Cristina Picchio, Eric Santos Martin, Rossano Cesari, George Adrian Calin, Sai Yendamuri, Tamotsu Kuroki, Francesca Pentimalli, Manuela Sarti, Kristine Yoder, Larry R. Kaiser, Richard Fishel, Carlo Maria Croce

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Parkin, a gene mutated in autosomal recessive juvenile Parkinsonism and mapped to the common fragile site FRA6E on human chromosome 6q25-q27, is associated with a frequent loss of heterozygosity and altered expression in breast and ovarian carcinomas. In addition, homozygous deletions of exon 2 creating deleterious truncations of the Parkin transcript were observed in the lung adenocarcinoma cell lines Calu-3 and H-1573, suggesting that the loss of this locus and the resulting changes in its expression are involved in the development of these tumors. Experimental Design: We examined 20 paired normal and non-small cell lung cancer samples for the presence of Parkin alterations in the coding sequence and changes in gene expression. We also restored gene expression in the Parkin-deficient lung carcinoma cell line H460 by use of a recombinant lentivirus containing the wild-type Parkin cDNA. Results: Loss of heterozygosity analysis identified a common region of loss in the Parkin/FRA6E locus with the highest frequency for the intragenic marker D6S1599 (45%), and semi-quantitative reverse transcription-PCR revealed reduced expression in 3 of 9 (33%) lung tumors. Although we did not observe any in vitro changes in cell proliferation or cell cycle, ectopic Parkin expression had the ability to reduce in vivo tumorigenicity in nude mice. Conclusion: These data suggest that Parkin is a tumor suppressor gene whose inactivation may play an important role in non-small cell lung cancer tumorigenesis.

Original languageEnglish
Pages (from-to)2720-2724
Number of pages5
JournalClinical Cancer Research
Volume10
Issue number8
DOIs
Publication statusPublished - Apr 15 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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