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

## TL;DR

This study explores how different APOBEC3 enzymes affect tumor progression in a breast cancer mouse model, finding that APOBEC3A and APOBEC3H promote tumor growth more than APOBEC3B.

## Contribution

The study reveals distinct functional consequences of APOBEC3A, APOBEC3B, and APOBEC3H Haplotype I on tumor progression in a breast cancer xenograft model.

## Key findings

- APOBEC3A-exposed cells with high expression increased tumor progression in mice.
- APOBEC3B-exposed cells with high expression decreased tumor size in mice.
- APOBEC3H Haplotype I-exposed cells stochastically increased tumor progression regardless of expression levels.

## Abstract

The APOBEC3 family of cytidine deaminases induces somatic mutations that are highly prevalent in cancers, but the functional consequences remain largely unknown.

To determine these consequences, we exposed MCF7 tumorigenic breast epithelial cells to APOBEC3A, APOBEC3B or APOBEC3H Haplotype I.

Comparative analysis between cells pre and post ‐APOBEC3 exposure revealed fewer deamination‐dependent γH2AX foci post‐APOBEC3 exposure, despite maintaining APOBEC3 protein expression. In a mouse xenograft model, high expressing, but not low expressing APOBEC3A‐exposed cells caused increased tumor progression. In contrast, high expressing, but not low expressing APOBEC3B‐exposed cells decreased tumor size. APOBEC3H Haplotype I‐exposed cells stochastically increased tumor progression independent of expression levels. Consistent with tumor data, RNA‐seq showed upregulation of tumor enhancing pathways only in cells that enhanced tumor progression.

The results indicate that in a breast cancer xenograft model, APOBEC3A and APOBEC3H Haplotype I are more likely to contribute to enhanced tumor progression than APOBEC3B.