# Association of Selected STAT Inhibitors with Prolactin-Induced Protein (PIP) in Breast Cancer

## TL;DR

This study explores how PIP and STAT5 inhibitors are connected in breast cancer, suggesting their potential roles in treatment response and prognosis.

## Contribution

The study reveals a novel link between PIP and STAT5 inhibitors, particularly nuclear PIAS3, in breast cancer progression and treatment sensitivity.

## Key findings

- PIP and STAT5 levels decrease with higher tumor grade, size, and clinical stage.
- Nuclear PIAS3 levels increase with tumor progression and correlate with PIP expression.
- T47D cells with higher PIP expression show increased sensitivity to doxorubicin.

## Abstract

Breast cancer (BC) is the most common cancer in women, and a higher level of prolactin-induced protein (PIP) is associated with better responses to adjuvant chemotherapy. The signal transducer and activator of transcription 5 (STAT5) is a potential regulator of the PIP gene. Prolactin (PRL) and its receptor (PRLR) activate JAK2/STAT5 signaling in BC, which is modulated by inhibitors like suppressors of cytokine signaling (SOCS) proteins and protein inhibitors of activated STAT (PIAS). Using real-time PCR and immunohistochemistry, we studied the relationship between PIP and STAT5 inhibitors in BC. Our findings indicated that PIP and STAT5 levels decrease with a higher tumor grade, size, and tumor/nodes/metastasis (TNM) clinical stage, while nuclear PIAS3 levels increase with tumor progression. Both STAT inhibitors are linked to estrogen and progesterone receptor status. Notably, STAT5 correlates positively with PIP, SOCS3, and PIAS3, suggesting that it may be a favorable prognostic factor. Among the STAT inhibitors, only nuclear PIAS3 expression correlates with PIP. In vitro studies indicated that silencing PIAS3 in T47D cells does not affect PIP expression or sensitivity to doxorubicin (DOX), but T47D control cells with a higher PIP expression are more sensitive to DOX, highlighting the need for further investigation into these mechanisms.