Background
We recently identified MUC1 as a target driving selection for 1q21 amplification and
validated it as an independent marker of aggressive behavior in thyroid cancer (TC).
The aims of this study were to determine whether TC cell lines retain MUC1 expression
patterns that are seen in primary tumors, assess the role of MUC1 in tumor maintenance,
and develop a virally delivered anti-MUC1 RNA interference (RNAi) that is effective
in decreasing MUC1 expression in vitro.
Methods
Fifteen TC cell lines were screened for MUC1 protein expression. Cell lines with varying
MUC1 protein levels were treated with anti-MUC1 monoclonal antibody to assess cell
viability. A recombinant retroviral short hairpin RNAi delivery system against MUC1
was developed. Efficacy and optimal dosing of short hairpin RNA against MUC1 was determined.
Results
MUC1 expression patterns in TC cell lines were found to be similar to that seen in
primary tumors. Treatment with anti-MUC1 antibody resulted in a significant decrease
in cell viability in MUC1 over-expressing cell lines. MUC1-779 RNAi construct showed
excellent infection efficiency and reproducible silencing.
Conclusion
These data offer functional evidence that implicates MUC1 over-expression as a key
molecular event in the pathogenesis of aggressive TC. Retrovirally delivered anti-MUC1
RNAi is effective in silencing MUC1 and merits further investigation to establish
therapeutic efficacy and safety in anticipation of potential clinical application.
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Article info
Publication history
Accepted:
September 22,
2005
New York, NYFootnotes
Presented at the 26th Annual Meeting of the American Association of Endocrine Surgeons, Cancun, Mexico, April, 2005.
Identification
Copyright
© 2005 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
