Suppression of the tumorigenic phenotype by chromosome 18 transfer into pancreatic cancer cell lines

Liviu P. Lefter, Toru Furukawa, Makoto Sunamura, Dan G. Duda, Kazunori Takeda, Noriko Kotobuki, Mitsuo Oshimura, Seiki Matsuno, Akira Horii

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

A number of lines of evidence have suggested that the long arm of chromosome 18 apart from SMAD4 may carry a tumor-suppressor gene(s) that plays a role in the early stage of pancreatic ductal carcinogenesis. Thus, adenovirus-mediated introduction of SMAD4 does not suppress in vitro growth in cells with completely inactivated SMAD4, and frequent loss of 18q at the SMAD4 locus is observed in pancreatic cancers but no abnormalities of the normal SMAD4 homolog have been detected. In this study, we introduced a normal copy of chromosome 18 into some pancreatic ductal carcinoma cells with and without a complete inactivation of SMAD4. Both anchorage-dependent and -independent proliferation as well as invasiveness were significantly suppressed in the hybrid clones compared with that of their parental cells. Moreover, significant suppression of tumorigenesis was observed after inoculation in nude mice, irrespective of the SMAD4 status. Our present study provides the first functional evidence of the existence of an additional tumor-suppressor gene(s), other than SMAD4 and DCC, that is responsible for the pathogenesis in the early stage of pancreatic ductal carcinogenesis.

Original languageEnglish
Pages (from-to)234-242
Number of pages9
JournalGenes Chromosomes and Cancer
Volume34
Issue number2
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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