Jack DuFauchard

Glucocorticoids, including dexamethasone, are common treatments for cancer patients experiencing side-effects of platinum-based chemotherapies. Previous research suggests that treatment with dexamethasone suppresses cancer cell death by apoptosis, undermining the efficacy of chemotherapy. Glucocorticoid receptors (GR) are ligand-activated transcription factors that promote survival of cancer cells. Recently, GR has emerged as a mediator of cancer metastasis. Transforming growth factor beta 1 (TGF𝛽1) is known to be similarly responsible for malignant tumor metastasis. Our lab recently discovered that TGF𝛽1, in the absence of GR ligands, phosphorylates GR on Ser134, an amino-terminal MAPK-consensus site residue, in triple-negative breast cancer (TNBC) cells. This event leads to transcriptional upregulation of a subset of GR-dependent genes required for cell motility, migration, and metabolic plasticity. Due to the genetic similarity of high grade serous ovarian cancer (OC) and TNBC, the purpose of this study was to explore ligand-independent activation of GR in OC. OVCAR8 cells were treated with TGF𝛽1 or dexamethasone in intervals of 15, 30, and 60 minutes. MDA-MB-231 TNBC cells were used as positive control. Protein lysates were separated by gel electrophoresis and blotted for pSer-134-GR, total GR and GAPDH. Following treatment with either TGF𝛽1 or dexamethasone, GR was rapidly phosphorylated on Ser134 as early as 15 min in OVCAR8 cells compared to vehicle control, suggesting that like TNBC cells, OC cells use GR-driven mechanisms to promote advanced cancer phenotypes. Future directions will determine if TGF𝛽1 induces upregulation of p-GR target genes (LEFTY2, PIP3K1) and promotes pro-survival, migration, altered metabolism, and metastasis in OC models.