title: A novel animal model for locally advanced breast cancer.
abstract: BACKGROUND
  Locally advanced breast cancer (LABC) poses complex management issues due to failure of response to chemotherapy and progression to local complications such as skin erosion, superinfection, and lymphedema. Most cell line and animal models are not adequate to study LABC.
  
  
  METHODS
  A patient-derived xenograft (IOWA-1T) from a patient with LABC was characterized for expression profile, short tandem repeat profile, oncogenic mutations, xenograft growth, and response to therapy.
  
  
  RESULTS
  Short tandem repeat profile authenticated the cell line as derived from a human woman. The primary tumor and derived xenografts were weakly estrogen receptor alpha positive (<5%), progesterone receptor negative, and HER2 nonamplified. Expression array profile compared to MCF-7 and BT-549 cell lines indicate that IOWA-1T was more closely related to basal breast cancer. IOWA-1T harbors a homozygous R248Q mutation of the TP53 gene; in vitro invasion assay was comparable to BT-549 and greater than MCF-7. IOWA-1T xenografts developed palpable tumors in 9.6 ± 1.6 days, compared to 49 ± 13 days for parallel experiments with BT-20 cells (p < 0.002). Tumor xenografts became locally advanced, growing to >2 cm in 21.6 ± 2 days, characterized by skin erosion necessitating euthanasia. The SUMO inhibitor anacardic acid inhibited the outgrowth of IOWA-1T xenografts, while doxorubicin had no effect on tumorigenesis.
  
  
  CONCLUSIONS
  IOWA-1T is a novel cell line with an expression pattern consistent with basal breast cancer. Xenografts recapitulated LABC and provide a novel model for testing therapeutic drugs that may be effective in cases resistant to conventional chemotherapy.
authors.affiliation: Department of Surgery, University of Iowa, Iowa City, IA, USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Bogachek
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Park
authors.forename: James P
authors.initials: JP
authors.lastname: De Andrade
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Kulak
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: White
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.forename: Philip M
authors.initials: PM
authors.lastname: Spanheimer
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Bair
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Olivier
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Weigel
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger