PTP1B INHIBITION IN HUMAN BREST CANCER CELL LINES WITH DIFFERENTIAL EXPRESSION OF HER2

CÓRDOBA EVELYN; REDONDO ANALIA L; LOSSINO ANTONELLA; FORD PAULA; NADIN SILVINA B; CUELLO-CARRIÓN DARIO; FANELLI MARIEL

Mendoza

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

The protein tyrosine phosphatase PTP1B plays an important role in breast cancer and is involved in the HER2 signaling pathway. Moreover, PTP1Bmodulates the association between N-cadherin and β-catenin. The aim of this study was to evaluate the role of inhibiting the phosphatase activity ofPTP1B in SKBR3 and MCF7 cells treated with Heregulin (Hrg), Trastuzumab (Tz), and/or α-Bromo-4-hydroxyacetophenone (PTPi). The changes inlocalization and expression of β-catenin and PTP1B were evaluated by immunofluorescence and Western blot. The viability in 3D cultures wasassessed 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 PTP1Binhibitor. 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.