PTP1B inhibition in human breast cancer cell lines with diferential expresion of HER2

CÓRDOBA M. E.; REDONDO A. L.; LOSSINO A. D.; FORD P.; NADIN S. B.; CUELLO CARRIÓN F. D.; FANELLI M. A.

San Luis

Congreso; XLII Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2024

Sociedad de Biología de Cuyo

The protein tyrosine phosphatase PTP1B plays an important role in breast cancer and is involved in the HER2 signaling pathway. Moreover, PTP1B modulates the association between N-cadherin and β-catenin. The aim of this study was to evaluate the role of inhibiting the phosphatase activity of PTP1B in SKBR3 and MCF7 cells treated with Heregulin (Hrg), Trastuzumab (Tz), and/or α-Bromo-4-hydroxyacetophenone (PTPi). The changes in localization and expression of β-catenin and PTP1B were evaluated by immunofluorescence and Western blot. The viability in 3D cultures was assessed using propidium iodide and calcein. In SKBR3 cells, PTP1B inhibition induced the distribution of PTP1B and β-catenin at the membrane, although no colocalization between them was observed. Only in SKBR3 cells the levels of β-catenin, PTP1B, and HER2 were affected by the PTP1B inhibitor. After 48-72 hours, only SKBR3 spheroids grew with Hrg and the number of dead cells increased in the presence of the inhibitor and Tz. These results suggest that PTP1B inhibition could enhance the inhibitory effect of trastuzumab on the HER2 pathway.