MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas.
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.


CONCLUSIONS
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.
Patel
Kepal N
KN
Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Maghami
Ellie
E
Wreesmann
Volkert B
VB
Shaha
Ashok R
AR
Shah
Jatin P
JP
Ghossein
Ronald
R
Singh
Bhuvanesh
B
D000941:Antigens / Q000502:physiology*; D000951:Antigens, Neoplasm; D002277:Carcinoma / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival; D018390:Gene Targeting; D005822:Genetic Vectors; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D018396:Mucin-1; D009077:Mucins / Q000502:physiology*; D034622:RNA Interference; D012190:Retroviridae; D013964:Thyroid Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000628:therapy
D000941:Antigens; D000951:Antigens, Neoplasm; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins