ATPase copper transporting beta attenuates malignant features with high expression as an indicator of favorable prognosis in breast cancer

TL;DR

High levels of ATP7B protein are linked to better outcomes in breast cancer patients and reduce cancer cell growth and spread.

Contribution

This study identifies ATP7B as a tumor suppressor and favorable prognostic marker in breast cancer.

Findings

ATP7B is highly expressed in certain breast cancer cell lines and correlates with tumor suppressor genes.

Reducing ATP7B increases cancer cell proliferation, migration, and invasion.

High ATP7B expression is associated with better prognosis in breast cancer patients.

Abstract

ATPase copper transporting beta (ATP7B) functions as a copper-transporting ATPase that ejects copper from cells. Although high expression of ATP7B has been reported to increase cisplatin resistance, its role in breast cancer (BC) remains unclear. This study aimed to elucidate the function of ATP7B in BC cells and its significance in patients with BC.

The mRNA and protein expression levels of ATP7B were evaluated in BC and non-cancerous mammary cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between ATP7B and 84 cancer-related genes. ATP7B knockdown was performed using small interfering RNA, and cell proliferation, invasiveness, and migration were analyzed. The associations between the mRNA and protein expression of ATP7B and clinicopathological factors were also investigated in 156 patients with BC.

ATP7B was found to be highly expressed in estrogen receptor-positive and human epidermal growth factor receptor 2-positive BC cell lines. PCR array analysis revealed a significant correlation between the expression level of ATP7B and those of cadherin 1, estrogen receptor 1, and MET proto-oncogene. ATP7B knockdown significantly increased the proliferation, invasiveness, and migration of MDA-MB-361 and MDA-MB-415 cells. Patients with high ATP7B expression at the mRNA and protein levels experienced favorable prognoses. In addition, ATP7B expression level was identified as an independent prognostic factor in multivariate analysis.

ATP7B is involved in promoting anti-cancer activities of tumor suppressors in BC cells across different subtypes and is considered a prognostic marker for BC.

The online version contains supplementary material available at 10.1007/s12282-025-01705-7.

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