Estradiol-Responsive miR-365a-3p Interacts with Tissue Factor 3'UTR to Modulate Tissue Factor-Initiated Thrombin Generation.

Background: High estradiol (E) levels are linked to an increased risk of venous thromboembolism; however, the underlying molecular mechanism(s) remain poorly understood. We previously identified an E-responsive microRNA (miR), miR-494-3p, that downregulates protein S expression, and posited additional coagulation factors, such as tissue factor, may be regulated in a similar manner via miRs.

Objectives: To evaluate the coagulation capacity of cohorts with high physiological E, and to further characterize novel E-responsive miR and miR regulation on tissue factor in E-related hypercoagulability.

ERK/MAPK regulation of the androgen responsiveness of breast cancer cells.

The androgen receptor (AR) is the most widely expressed steroid hormone receptor in human breast cancers and androgens including 5alpha-dihydrotestosterone are potent inhibitors of breast cancer cell proliferation. The extracellular signal-regulated mitogen activated protein kinase (ERK/MAPK) pathway is hyperactivated in a proportion of breast tumors and can interact with steroid hormone receptor signaling by altering receptor phosphorylation, turnover, ligand, and cofactor interactions. To examine the effects of ERK/ MAPK hyperactivity on AR levels, MCF-7 cells were stably transfected with a plasmid encoding a constitutively active MEK1 protein to create MCF-7-DeltaMEK1 cells.