Differential effects on tumor progression by APOBEC3A, APOBEC3B, and APOBEC3H Haplotype I in a breast cancer mouse

Milaid Granadillo Rodríguez1, Lai Wong1, Arzhang Shayeganmehr1

  • 1Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

Frontiers in Genetics
|February 12, 2026
PubMed
Abstract

Insights

The APOBEC3 family of cytidine deaminases impacts cancer progression. APOBEC3A and APOBEC3H increased tumor growth, while APOBEC3B reduced it in a breast cancer model.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3) family of cytidine deaminases is known to induce somatic mutations in cancer.
  • However, the functional implications of these mutations and the specific roles of individual APOBEC3 members in cancer progression are not well understood.

Purpose of the Study:

  • To investigate the functional consequences of APOBEC3A, APOBEC3B, and APOBEC3H Haplotype I exposure on breast cancer cells and tumor progression.
  • To determine how different APOBEC3 members influence tumor growth and associated molecular pathways.

Main Methods:

  • MCF7 tumorigenic breast epithelial cells were exposed to APOBEC3A, APOBEC3B, or APOBEC3H Haplotype I.
  • Comparative analysis of DNA damage markers (γH2AX foci) was performed pre- and post-APOBEC3 exposure.
  • A mouse xenograft model was used to assess tumor progression in response to APOBEC3 exposure.
  • RNA sequencing (RNA-seq) was employed to analyze gene expression changes in exposed cells.

Main Results:

  • APOBEC3 exposure led to fewer deamination-dependent γH2AX foci, despite sustained APOBEC3 protein expression.
  • High expression of APOBEC3A correlated with increased tumor progression in the mouse xenograft model.
  • High expression of APOBEC3B correlated with decreased tumor size.
  • APOBEC3H Haplotype I exposure resulted in stochastic increases in tumor progression, irrespective of expression levels.
  • RNA-seq data revealed upregulation of tumor-enhancing pathways specifically in cells that showed enhanced tumor progression.

Conclusions:

  • APOBEC3A and APOBEC3H Haplotype I are more likely to promote tumor progression in a breast cancer xenograft model compared to APOBEC3B.
  • The differential effects of APOBEC3 family members highlight their complex roles in cancer development and progression.

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