MiR-221 confers lapatinib resistance by negatively regulating p27^kip1 in HER2-positive breast cancer.

ABSTRACT: Development of acquired resistance to lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor, severely limits the duration of clinical response in advanced HER2-driven breast cancer patients. Although the compensatory activation of the PI3K/Akt survival signal has been proposed to cause acquired lapatinib resistance, comprehensive molecular mechanisms remain required to develop more efficient strategies to circumvent this therapeutic difficulty. In this study, we found that suppression of HER2 by lapatinib still led to Akt inactivation and elevation of FOX3a protein levels, but failed to induce the expression of their downstream pro-apoptotic effector p27^kip1 , a cyclin-dependent kinase inhibitor. Eleva

SUBMITTER: Huynh TK 

PROVIDER: S-EPMC8486195 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature