Antisense RNA to the putative tumor-suppressor gene DCC transforms Rat-1 fibroblasts Journal Article


Authors: Narayanan, R.; Lawlor, K. G.; Schaapveld, R. Q. J.; Cho, K. R.; Vogelstein, B.; Tran, P. B. V.; Osborne, M. P.; Telang, N. T.
Article Title: Antisense RNA to the putative tumor-suppressor gene DCC transforms Rat-1 fibroblasts
Abstract: Allelic deletions involving chromosomes 18q occur in a significant number of colorectal cancers. Recently, a highly conserved gene called 'deleted in colorectal cancer' (DCC) has been identified on chromosome 18q. DCC has been postulated to be a colorectal tumor-suppressor gene. In order to understand the role of DCC in cell transformation, we have established a stable Rat-1 cell line expressing dexamethasone-inducible DCC antisense RNA. High levels of dexamethasone-inducible DCC antisense RNA were detected in the Rat-1 transfectants. The antisense DCC-expressing Rat-1 cells showed a faster growth rate, anchorage independence and tumorigenicity in nude mice. Exposure of the parental Rat-1 cells to antisense oligodeoxyribonucleotides to DCC resulted in inhibition of cell adhesion to the substratum which could be abrogated by various extracellular matrices. On the other hand, a bone marrow-derived stromal cell line which does not express DCC showed no detachment from the substratum when treated with the antisense oligo to DCC. These results suggest that the DCC gene is involved in cell adhesion and provide the first direct biological evidence for the possible role of DCC as a tumor-suppressor gene.
Keywords: c-myc; growth-factor; wilms tumor; cell-adhesion; proto-oncogene; thymidine kinase gene; osteo-sarcoma; anti-sense rna; human retinoblastoma gene; myc expression
Journal Title: Oncogene
Volume: 7
Issue: 3
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 1992-03-01
Start Page: 553
End Page: 561
Language: English
ACCESSION: WOS:A1992HK00500023
PROVIDER: wos
PUBMED: 1549369
Notes: Article -- Source: Wos
Citation Impact
MSK Authors
  1. Michael P. Osborne
    61 Osborne
  2. Nitin Telang
    29 Telang