Effect of inhibiting autophagy induced by PTEN loss on intrinsic breast cancer resistance to trastuzumab therapy.

e11532 Background: This study determined the effects of the phosphatase and tensin homolog (PTEN) expression level on autophagic status and on breast cancer's de novo resistance to trastuzumab. Methods: The correlation between PTEN and trastuzumab resistance from clinical specimens were detected using immunochemistry and western blot. Estrogen receptor (ER)-expressing breast cancer cell lines were treated with shRNA expression vectors directed against PTEN mRNA and control vectors respectively, effects on autophagy signal transduction pathways and growth of tumors in an orthotopic nude mouse model were determined. The orthotopically implanted model of breast cancer was established using trastuzumab-resistant HER2-expressing breast cancer cells. The expression of autophagy-related proteins (LC3 I/II, p62, LAMP and cathepsin B) was determined by western blot analysis. Cell viability was determined via MTT assay. Results: Down-regulation of PTEN and autophagic proteins LC3-I and -II was observed in non-resis...