LMTK3 is implicated in endocrine resistance via multiple signaling pathways

摘要: Resistance to endocrine therapy in breast cancer is common. With the aim of discovering new molecular targets for therapy, we have recently identified LMTK3 as a regulator estrogen receptor-alpha (ERα) and wished understand its role resistance. We find that inhibition xenograft tamoxifen (Tam)-resistant (BT474) mouse model results re-sensitization Tam demonstrated by reduction tumor volume. A whole genome microarray analysis, using BT474 cell line, reveals genes significantly modulated (positively or negatively) after silencing, including some are known be implicated resistance, notably c-MYC, HSPB8 SIAH2. show able increase levels at transcriptional translational level thereby protecting MCF7 cells from Tam-induced death, reducing autophagy. Finally, high baseline tumors predictive resistance; does not lead alteration levels, whereas patient's plasma samples, acquired gene amplification (copy number variation) was associated with relapse while receiving Tam. In aggregate, these data support both innate (intrinsic) (adaptive) resistance cancer.