MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas

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, as...

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Published in:Surgery 2005-12, Vol.138 (6), p.994-1002
Main Authors: Patel, Kepal N., Maghami, Ellie, Wreesmann, Volkert B., Shaha, Ashok R., Shah, Jatin P., Ghossein, Ronald, Singh, Bhuvanesh
Format: Article
Language:English
Subjects:
Antigens - physiology
Antigens, Neoplasm
Carcinoma - etiology
Carcinoma - metabolism
Carcinoma - therapy
Cell Culture Techniques
Cell Line, Tumor
Cell Survival
Gene Targeting
Genetic Vectors
Glycoproteins - physiology
Humans
Mucin-1
Mucins - physiology
Retroviridae
RNA Interference
Thyroid Neoplasms - etiology
Thyroid Neoplasms - metabolism
Thyroid Neoplasms - therapy
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Summary: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. 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. 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. 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.
ISSN:0039-6060
1532-7361
DOI:10.1016/j.surg.2005.09.030