MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas

Kepal N. Patel, Ellie Maghami, Volkert B. Wreesmann, Ashok R. Shaha, Jatin P. Shah, Ronald Ghossein, Bhuvanesh Singh, Thomas J. Fahey, Martha A. Zeiger, Gerard M. Doherty, Orlo H. Clark

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)994-1002
Number of pages9
JournalSurgery
Volume138
Issue number6
DOIs
StatePublished - Dec 2005
Externally publishedYes

Fingerprint

Thyroid Neoplasms
RNA Interference
Maintenance
Cell Line
Neoplasms
Small Interfering RNA
Cell Survival
Anti-Idiotypic Antibodies
Proteins
Monoclonal Antibodies
Safety
Infection
Therapeutics

ASJC Scopus subject areas

  • Surgery

Cite this

Patel, K. N., Maghami, E., Wreesmann, V. B., Shaha, A. R., Shah, J. P., Ghossein, R., ... Clark, O. H. (2005). MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas. Surgery, 138(6), 994-1002. https://doi.org/10.1016/j.surg.2005.09.030

MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas. / Patel, Kepal N.; Maghami, Ellie; Wreesmann, Volkert B.; Shaha, Ashok R.; Shah, Jatin P.; Ghossein, Ronald; Singh, Bhuvanesh; Fahey, Thomas J.; Zeiger, Martha A.; Doherty, Gerard M.; Clark, Orlo H.

In: Surgery, Vol. 138, No. 6, 12.2005, p. 994-1002.

Research output: Contribution to journalArticle

Patel, KN, Maghami, E, Wreesmann, VB, Shaha, AR, Shah, JP, Ghossein, R, Singh, B, Fahey, TJ, Zeiger, MA, Doherty, GM & Clark, OH 2005, 'MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas', Surgery, vol. 138, no. 6, pp. 994-1002. https://doi.org/10.1016/j.surg.2005.09.030
Patel KN, Maghami E, Wreesmann VB, Shaha AR, Shah JP, Ghossein R et al. MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas. Surgery. 2005 Dec;138(6):994-1002. https://doi.org/10.1016/j.surg.2005.09.030
Patel, Kepal N. ; Maghami, Ellie ; Wreesmann, Volkert B. ; Shaha, Ashok R. ; Shah, Jatin P. ; Ghossein, Ronald ; Singh, Bhuvanesh ; Fahey, Thomas J. ; Zeiger, Martha A. ; Doherty, Gerard M. ; Clark, Orlo H. / MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas. In: Surgery. 2005 ; Vol. 138, No. 6. pp. 994-1002.
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abstract = "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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AU - Patel, Kepal N.

AU - Maghami, Ellie

AU - Wreesmann, Volkert B.

AU - Shaha, Ashok R.

AU - Shah, Jatin P.

AU - Ghossein, Ronald

AU - Singh, Bhuvanesh

AU - Fahey, Thomas J.

AU - Zeiger, Martha A.

AU - Doherty, Gerard M.

AU - Clark, Orlo H.

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N2 - 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.

AB - 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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