A Novel Animal Model for Locally Advanced Breast Cancer

Maria V Bogachek; Jung Min Park; James P De Andrade; Mikhail V Kulak; Jeffrey R White; Tong Wu; Philip M Spanheimer; Thomas B Bair; Alicia K Olivier; Ronald J Weigel

doi:10.1245/s10434-014-4174-8

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A Novel Animal Model for Locally Advanced Breast Cancer

Journal article

Open access

Peer reviewed

A Novel Animal Model for Locally Advanced Breast Cancer

Maria V Bogachek, Jung Min Park, James P De Andrade, Mikhail V Kulak, Jeffrey R White, Tong Wu, Philip M Spanheimer, Thomas B Bair, Alicia K Olivier and Ronald J Weigel

Annals of surgical oncology, Vol.22(3), pp.866-873

03/2015

DOI: 10.1245/s10434-014-4174-8

PMCID: PMC4425290

PMID: 25326397

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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.

Breast Cancer

Sumoylation

Cell Line

Locally-advanced

Animal Model

Details

Title: Subtitle: A Novel Animal Model for Locally Advanced Breast Cancer
Creators: Maria V Bogachek - Department of Surgery, University of Iowa, Iowa City, IA, USA
Jung Min Park - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA, USA
James P De Andrade - Department of Surgery, University of Iowa, Iowa City, IA, USA
Mikhail V Kulak - Department of Surgery, University of Iowa, Iowa City, IA, USA
Jeffrey R White - Department of Surgery, University of Iowa, Iowa City, IA, USA
Tong Wu - Department of Surgery, University of Iowa, Iowa City, IA, USA
Philip M Spanheimer - Department of Surgery, University of Iowa, Iowa City, IA, USA
Thomas B Bair - Iowa Institute for Human Genetics, University of Iowa, Iowa City, IA, USA
Alicia K Olivier - Department of Pathology, University of Iowa, Iowa City, IA, USA
Ronald J Weigel - Department of Surgery, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Annals of surgical oncology, Vol.22(3), pp.866-873
DOI: 10.1245/s10434-014-4174-8
PMID: 25326397
PMCID: PMC4425290
NLM abbreviation: Ann Surg Oncol
ISSN: 1068-9265
eISSN: 1534-4681
Language: English
Date published: 03/2015
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984025285302771

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