Detailed molecular fingerprinting of four new anaplastic thyroid carcinoma cell lines and their use for verification of RhoB as a molecular therapeutic target

Laura A. Marlow, Jaclyn D'Innocenzi, Yilin Zhang, Stephen D. Rohl, Simon J. Cooper, Thomas Sebo, Clive Grant, Bryan McIver, Jan Kasperbauer, J. Trad Wadsworth, John D. Casler, Pamela W. Kennedy, W Edward Jr. Highsmith, Orlo Clark, Dragana Milosevic, Brian Netzel, Kendall Cradic, Shilpi Arora, Christian Beaudry, Stefan K. GrebeMarc L. Silverberg, David O. Azorsa, Robert Christian Smallridge, John A III Copland

Research output: Contribution to journalArticle

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Abstract

Context: Anaplastic thyroid carcinoma (ATC) is a highly aggressive carcinoma in need of therapeutic options. One critical component of drug discovery is the availability of well-characterized cell lines for identification of molecular mechanisms related to tumor biology and drug responsiveness. Up to 42% of human thyroid cancer cell lines are redundant or not of correct tissue origin, and a comprehensive analysis is currently nonexistent. Mechanistically, RhoB has been identified as a novel molecular target for ATC therapy. Objective: The aim was to develop four ATC cell lines detailing genetic, molecular, and phenotypic characteristics and to test five classes of drugs on the cell lines to determine whether they inhibited cell proliferation in a RhoB-dependent fashion. Design: Four cell lines were derived from ATC tumors. Short tandem DNA repeat and mutational status of the originating tumors and cell lines were performed along with molecular and phenotypic characterizations. Compounds were tested for growth inhibition and ability to up-regulate RhoB. Results: Cell line authenticity was confirmed by DNA short tandem repeat analysis. Each proved unique regarding expression of thyroid markers, oncogene status, amplified and deleted genes, and proliferative growth rates. FTI-277, GGTI-286, lovastatin, romidepsin, and UCN-01 up-regulated RhoB and inhibited cell proliferation in a dose-responsive fashion with only romidepsin and FTI-277 being RhoB dependent. Conclusions: Molecular descriptions of thyroid lines were matched to the originating tumors, setting a new standard for cell line characterization. Furthermore, suppressed RhoB is implicated as a molecular target for therapy against ATC because five classes of drugs up-regulate RhoB and inhibit growth dose-responsively.

Original languageEnglish (US)
Pages (from-to)5338-5347
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume95
Issue number12
DOIs
StatePublished - Dec 2010

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Cells
Cell Line
Tumors
Cell proliferation
Microsatellite Repeats
Therapeutics
Thyroid Gland
Up-Regulation
Growth
Cell Proliferation
Pharmaceutical Preparations
Lovastatin
Neoplasms
DNA
Drug Discovery
Anaplastic Thyroid Carcinoma
Tumor Cell Line
Oncogenes
Thyroid Neoplasms
Molecular Biology

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Detailed molecular fingerprinting of four new anaplastic thyroid carcinoma cell lines and their use for verification of RhoB as a molecular therapeutic target. / Marlow, Laura A.; D'Innocenzi, Jaclyn; Zhang, Yilin; Rohl, Stephen D.; Cooper, Simon J.; Sebo, Thomas; Grant, Clive; McIver, Bryan; Kasperbauer, Jan; Wadsworth, J. Trad; Casler, John D.; Kennedy, Pamela W.; Highsmith, W Edward Jr.; Clark, Orlo; Milosevic, Dragana; Netzel, Brian; Cradic, Kendall; Arora, Shilpi; Beaudry, Christian; Grebe, Stefan K.; Silverberg, Marc L.; Azorsa, David O.; Smallridge, Robert Christian; Copland, John A III.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 95, No. 12, 12.2010, p. 5338-5347.

Research output: Contribution to journalArticle

Marlow, LA, D'Innocenzi, J, Zhang, Y, Rohl, SD, Cooper, SJ, Sebo, T, Grant, C, McIver, B, Kasperbauer, J, Wadsworth, JT, Casler, JD, Kennedy, PW, Highsmith, WEJ, Clark, O, Milosevic, D, Netzel, B, Cradic, K, Arora, S, Beaudry, C, Grebe, SK, Silverberg, ML, Azorsa, DO, Smallridge, RC & Copland, JAIII 2010, 'Detailed molecular fingerprinting of four new anaplastic thyroid carcinoma cell lines and their use for verification of RhoB as a molecular therapeutic target', Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 12, pp. 5338-5347. https://doi.org/10.1210/jc.2010-1421
Marlow, Laura A. ; D'Innocenzi, Jaclyn ; Zhang, Yilin ; Rohl, Stephen D. ; Cooper, Simon J. ; Sebo, Thomas ; Grant, Clive ; McIver, Bryan ; Kasperbauer, Jan ; Wadsworth, J. Trad ; Casler, John D. ; Kennedy, Pamela W. ; Highsmith, W Edward Jr. ; Clark, Orlo ; Milosevic, Dragana ; Netzel, Brian ; Cradic, Kendall ; Arora, Shilpi ; Beaudry, Christian ; Grebe, Stefan K. ; Silverberg, Marc L. ; Azorsa, David O. ; Smallridge, Robert Christian ; Copland, John A III. / Detailed molecular fingerprinting of four new anaplastic thyroid carcinoma cell lines and their use for verification of RhoB as a molecular therapeutic target. In: Journal of Clinical Endocrinology and Metabolism. 2010 ; Vol. 95, No. 12. pp. 5338-5347.
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abstract = "Context: Anaplastic thyroid carcinoma (ATC) is a highly aggressive carcinoma in need of therapeutic options. One critical component of drug discovery is the availability of well-characterized cell lines for identification of molecular mechanisms related to tumor biology and drug responsiveness. Up to 42{\%} of human thyroid cancer cell lines are redundant or not of correct tissue origin, and a comprehensive analysis is currently nonexistent. Mechanistically, RhoB has been identified as a novel molecular target for ATC therapy. Objective: The aim was to develop four ATC cell lines detailing genetic, molecular, and phenotypic characteristics and to test five classes of drugs on the cell lines to determine whether they inhibited cell proliferation in a RhoB-dependent fashion. Design: Four cell lines were derived from ATC tumors. Short tandem DNA repeat and mutational status of the originating tumors and cell lines were performed along with molecular and phenotypic characterizations. Compounds were tested for growth inhibition and ability to up-regulate RhoB. Results: Cell line authenticity was confirmed by DNA short tandem repeat analysis. Each proved unique regarding expression of thyroid markers, oncogene status, amplified and deleted genes, and proliferative growth rates. FTI-277, GGTI-286, lovastatin, romidepsin, and UCN-01 up-regulated RhoB and inhibited cell proliferation in a dose-responsive fashion with only romidepsin and FTI-277 being RhoB dependent. Conclusions: Molecular descriptions of thyroid lines were matched to the originating tumors, setting a new standard for cell line characterization. Furthermore, suppressed RhoB is implicated as a molecular target for therapy against ATC because five classes of drugs up-regulate RhoB and inhibit growth dose-responsively.",
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T1 - Detailed molecular fingerprinting of four new anaplastic thyroid carcinoma cell lines and their use for verification of RhoB as a molecular therapeutic target

AU - Marlow, Laura A.

AU - D'Innocenzi, Jaclyn

AU - Zhang, Yilin

AU - Rohl, Stephen D.

AU - Cooper, Simon J.

AU - Sebo, Thomas

AU - Grant, Clive

AU - McIver, Bryan

AU - Kasperbauer, Jan

AU - Wadsworth, J. Trad

AU - Casler, John D.

AU - Kennedy, Pamela W.

AU - Highsmith, W Edward Jr.

AU - Clark, Orlo

AU - Milosevic, Dragana

AU - Netzel, Brian

AU - Cradic, Kendall

AU - Arora, Shilpi

AU - Beaudry, Christian

AU - Grebe, Stefan K.

AU - Silverberg, Marc L.

AU - Azorsa, David O.

AU - Smallridge, Robert Christian

AU - Copland, John A III

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N2 - Context: Anaplastic thyroid carcinoma (ATC) is a highly aggressive carcinoma in need of therapeutic options. One critical component of drug discovery is the availability of well-characterized cell lines for identification of molecular mechanisms related to tumor biology and drug responsiveness. Up to 42% of human thyroid cancer cell lines are redundant or not of correct tissue origin, and a comprehensive analysis is currently nonexistent. Mechanistically, RhoB has been identified as a novel molecular target for ATC therapy. Objective: The aim was to develop four ATC cell lines detailing genetic, molecular, and phenotypic characteristics and to test five classes of drugs on the cell lines to determine whether they inhibited cell proliferation in a RhoB-dependent fashion. Design: Four cell lines were derived from ATC tumors. Short tandem DNA repeat and mutational status of the originating tumors and cell lines were performed along with molecular and phenotypic characterizations. Compounds were tested for growth inhibition and ability to up-regulate RhoB. Results: Cell line authenticity was confirmed by DNA short tandem repeat analysis. Each proved unique regarding expression of thyroid markers, oncogene status, amplified and deleted genes, and proliferative growth rates. FTI-277, GGTI-286, lovastatin, romidepsin, and UCN-01 up-regulated RhoB and inhibited cell proliferation in a dose-responsive fashion with only romidepsin and FTI-277 being RhoB dependent. Conclusions: Molecular descriptions of thyroid lines were matched to the originating tumors, setting a new standard for cell line characterization. Furthermore, suppressed RhoB is implicated as a molecular target for therapy against ATC because five classes of drugs up-regulate RhoB and inhibit growth dose-responsively.

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