title: Detailed molecular fingerprinting of four new anaplastic thyroid carcinoma cell lines and their use for verification of RhoB as a molecular therapeutic target.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Mayo Clinic, Department of Cancer Biology, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Marlow
authors.forename: Jaclyn
authors.initials: J
authors.lastname: D'Innocenzi
authors.forename: Yilin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Rohl
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Cooper
authors.forename: Thomas
authors.initials: T
authors.lastname: Sebo
authors.forename: Clive
authors.initials: C
authors.lastname: Grant
authors.forename: Bryan
authors.initials: B
authors.lastname: McIver
authors.forename: Jan L
authors.initials: JL
authors.lastname: Kasperbauer
authors.forename: J Trad
authors.initials: JT
authors.lastname: Wadsworth
authors.forename: John D
authors.initials: JD
authors.lastname: Casler
authors.forename: Pamela W
authors.initials: PW
authors.lastname: Kennedy
authors.forename: W Edward
authors.initials: WE
authors.lastname: Highsmith
authors.forename: Orlo
authors.initials: O
authors.lastname: Clark
authors.forename: Dragana
authors.initials: D
authors.lastname: Milosevic
authors.forename: Brian
authors.initials: B
authors.lastname: Netzel
authors.forename: Kendall
authors.initials: K
authors.lastname: Cradic
authors.forename: Shilpi
authors.initials: S
authors.lastname: Arora
authors.forename: Christian
authors.initials: C
authors.lastname: Beaudry
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Grebe
authors.forename: Marc L
authors.initials: ML
authors.lastname: Silverberg
authors.forename: David O
authors.initials: DO
authors.lastname: Azorsa
authors.forename: Robert C
authors.initials: RC
authors.lastname: Smallridge
authors.forename: John A
authors.initials: JA
authors.lastname: Copland
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005434:Flow Cytometry; D005819:Genetic Markers; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D014162:Transfection; D020743:rhoB GTP-Binding Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D005819:Genetic Markers; D020743:rhoB GTP-Binding Protein; D004121:Dimethyl Sulfoxide
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