Role of PTP1B phosphatase in the co expression of beta catenin and HER2 in the cytoplasmic membrane in HER2+ breast cancer cells

MARIA EVELYN CÓRDOBA; MARIA CELESTE RUETE; GISELA PENNACCHIO; JUAN MANUEL FERNANDEZ MUÑOZ; MARIEL A FANELLI

Workshop; 2nd International Workshop on Translational Cancer Research; 2021

Background and aims: The location of β-catenin has been associated with theprognosis of human breast cancer (BC). Direct interaction between β-catenin andHER2 receptor has been reported. Our previous studies showed that HER2-positivepatients with β-catenin expression in the plasma membrane and without trastuzumab(Tzb) therapy had significantly better survival. The protein tyrosine phosphatasePTP1B plays an important role in BC and is required for Her2/Neu-driven BC in mice.PTP1B binds to β-catenin keeping it located in the plasma membrane. The aim ofthis study was to evaluate the role of PTP1B in locating β-catenin and HER2 in thecell membrane of BC cells with different expression of HER2.Methodology: Protein expression and localization were evaluated by western blotand immunofluorescence in MCF7 and SKBR3 cells in response to Heregulin andTrastuzumab treatment. Copy number variation (CNV) of β-catenin (CTNNB1) andPTP1B (PTPN1) analysis from HER2 enriched BC patients were performed using theTCGA database.Results: SKBR3 cell line was more sensitive to trastuzumab than MCF7. β-cateninwas localized in the cell membrane of the both untreated cell lines. Heregulinpromoted perinuclear translocation of β-catenin,and decreased PTP1B expression.Trastuzumab preserved the cell membrane distribution of β-catenin and increasedPTP1B levels. Total expression of HER2 decreased with both treatments, while itsphosphorylated variant increased with heregulin and tended to decrease withtrastuzumab. The inhibition of PTP1B with α-Bromo-4-hydroxyacetophenoneincreased the levels of phospho-HER2 and β-catenin in MCF7 cells. PTPN1 had atendency to be amplified in HER2+ patients while CTNNB1 is downregulado. Also,these genetic changes were associated with the expression levelsDiscussion and Conclusions:This study shows that, the CNV of genetic variationhas a direct effect on mRNA levels of PTP1B and β-catenin in HER2 subtype BC.HER2 seems to be another target of PTP1B in MCF7 cell line.