# Response Gene to Complement 32 promotes cell proliferation and tamoxifen resistance in breast cancer via elevated FoxM1 expression

## TL;DR

This study shows that RGC-32 promotes breast cancer growth and tamoxifen resistance by increasing FoxM1 expression, suggesting it could be a new target for treatment.

## Contribution

The novel finding is that RGC-32 contributes to tamoxifen resistance in breast cancer via FoxM1 and ERα activation.

## Key findings

- RGC-32 overexpression leads to tamoxifen resistance in breast cancer cells.
- RGC-32 activates the PI3K pathway and enhances ERα activity to upregulate FoxM1.
- Knockdown of RGC-32 restores tamoxifen sensitivity in resistant cells.

## Abstract

Despite the high sensitivity of estrogen receptor positive (ER+) breast cancer to endocrine therapy, many patients have primary resistance or develop resistance to endocrine therapies. Acquired resistance to endocrine therapy is a great challenge in the treatment of ER+ breast cancer patient. Here we showed that Response Gene to Complement (RGC)-32 expression is higher in breast cancer than paired normal tissues, which was a poor predictive factor. RGC-32 overexpression resulted in tamoxifen resistance, whereas knockdown of RGC-32 in tamoxifen-resistant cells restored tamoxifen sensitivity. Tamoxifen resistance mediated by RGC-32 was shown to be partially dependent on FoxM1 expression. Mechanistically, RGC-32 could activated PI3K signaling pathway, and then enhanced estrogen receptor alpha (ERα) activity. ERα activation is essential for RGC-32-mediated the expression of FoxM1. These data support that targeting RGC-32 could effectively mitigate cancer progression and tamoxifen resistance, offering a complementary therapeutic approach to reduce acquired endocrine resistance.