The Proportion of Esophageal Adenocarcinoma Patients With Prior Barrett's Esophagus: Results From a Large Population Based Cohort

Introduction:Previous micro array studies and validation with Rt-PCR in a patient cohort from our group have shown that GDF 15 is up regulated in BE. GDF15 is a member of the transforming growth factor-beta superfamily which includes TGF-beta and BMP ligands and may be involved in regulation of tissue differentiation and maintenance. TGF-beta and BMP ligands signal through cell receptors inducing Smad activation. Activated Smad 2/3 builds a complex with Smad 4. The activated Smad-complex accumulates in the nucleus and can initiate gene expression. This transcriptional cascade appears crucial in cell transformation and differentiation as seen in BE. The aim was to examine the signaling potential of GDF15 in this cascade. Methods: Recombinant human GDF15 was used in stimulating Het1a cells (human esophageal squamous epithelial cell line). Smad activation into the nucleus was measured with immunostaining using Smad 1/2/3 antibodies and their nuclear intensity after stimulation. The intensity of activated Smad in the nucleus and quantitative amount of GDF15 utilizing Rt-PCR in Oe 33 cells (esophageal cancer cell line) was measured and then compared with levels in HET1a cells. Results: We found that stimulation of Het1a cells with GDF 15 leads to a time and dose dependant Smad activation. We established that optimal induction of Smad activation in Het1a cells is at 5 ng/ml with GDF15 for 1 h (p