Adv Pharm Bull. 2020;10(2): 323-328.
doi: 10.34172/apb.2020.039
PMID: 32373503
PMCID: PMC7191227
Scopus ID: 85088709108
  Abstract View: 416
  PDF Download: 290

Research Article

Expression of Diverse Angiogenesis Factor in Different Stages of the 4T1 Tumor as a Mouse Model of Triple-Negative Breast Cancer

Saba Malekian 1,2 ORCID logo, Marveh Rahmati 1 ORCID logo, Soyar Sari 2 ORCID logo, Monireh Kazemimanesh 3 ORCID logo, Raheleh Kheirbakhsh 1 ORCID logo, Ahad Muhammadnejad 1 ORCID logo, Saeid Amanpour 1* ORCID logo

1 Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
2 Department of Molecular and Cellular Sciences, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
3 Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran.


Purpose: Triple-negative breast cancer (TNBC) is specified by high vascularity and repetitious metastasis. Although several studies have indicated that angiogenesis has an important role in invasive breast cancer, a suitable model of TNBC that can show the exact onset of angiogenesis factors still needs to be developed. The purpose of this study is to determine the expression level of angiogenesis factors in different clinical stages of the 4T1 tumor as TNBC mouse model.

Methods: Twenty mice were injected by the 4T1 cell line, and four mice selected as healthy controls. Following by tumor induction, the mice were randomly put into four groups, each contains four mice. Once the tumor volume reached to the early stage (<100 mm3 ), intermediate stage (100-300 mm3 ), advanced stage (300-500 mm3 ), and end stage (>500 mm3 ), they were removed by surgery. Then, the expression levels of Hif1α, VEGFR1, and VEGFR2 genes, as well as tumor markers of VEGF, bFGF and CD31, were evaluated by qPCR and immunohistochemistry (IHC) respectively. The statistical analysis was done by SPSS version 16.

Results: TNBC tumors were confirmed and multi-foci metastasis in the lung were seen. The mRNA and protein expression levels of the angiogenesis factors increased in the early stage and as the tumor grew, their expression level enhanced dramatically.

Conclusion: The 4T1 syngeneic mouse tumor may serve as an appropriate TNBC model for further investigation of the angiogenesis and therapies. Moreover, angiogenesis factors are induced before the advanced stage, and anti-angiogenesis therapy is necessary to be considered at the first line of treatment in TBNC.

Keywords: Angiogenesis factor, bFGF, CD31, Triple-negative breast cancer, VEGF, VEGFR1, VEGFR2
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Submitted: 22 Jul 2019
Revision: 21 Sep 2019
Accepted: 30 Sep 2019
ePublished: 18 Feb 2020
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