Anti-LIFR polyclonal antibody

The signaling mechanisms regulating pluripotency in porcine embryonic stem cells and embryos are unknown. In this study, we characterize cell signaling in the in-vivo porcine inner cell mass and later-stage epiblast. We evaluate expression of OCT4, NANOG, SOX2, genes within the JAK/STAT pathway (LIF, LIFR, GP130), FGF pathway (bFGF, FGFR1, FGFR2), BMP pathway (BMP4), and downstream-activated genes (STAT3, c-Myc, c-Fos, and SMAD4). We discovered two different expression profiles exist in the developing porcine embryo. The D6 porcine blastocyst (inner cell mass stage) is devoid in the expression of most genes analyzed, with the exception of OCT4. In contrast, the D11 epiblast expressed 10 of the 12 genes investigated. Immunocytochemistry confirmed LIFR and bFGF was not expressed in the epiblast, but within the trophectoderm. These findings reveal cell signaling associated with maintaining pluripotency in human embryonic stem cells is detectable in the porcine epiblast, but not in the inner cell mass. Developmental Dynamics 238.2014-2024, 2009. (C) 2009 Wiley-Liss, Inc.

Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate that has been approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Despite the remarkable efficacy of T-DM1 in many patients, resistance to this therapeutic has emerged as a significant clinical problem. In the current study, we used BT-474/KR cells, a T-DM1-resistant cell line established from HER2-positive BT-474 breast cancer cells, as a model to investigate mechanisms of T-DM1 resistance and explore effective therapeutic regimens. We show here for the first time that activation of signal transducer and activator of transcription 3 (STAT3) mediated by leukemia inhibitory factor receptor (LIFR) overexpression confers resistance to T-DM1. Moreover, secreted factors induced by activated STAT3 in resistant cells limit the responsiveness of cells that were originally sensitive to T-DM1. Importantly, STAT3 inhibition sensitizes resistant cells to T-DM1, both in vitro and in vivo, suggesting that the combination T-DM1 with STAT3-targeted therapy is a potential treatment for T-DM1-refractory patients.