The Role of Tumor Microenvironment in the Progression of Prostate Cancer

Abstract

My research aims to investigate how reactive oxygen species(ROS) induced transcription factors NFKB, ATF-2 and RUNX-2 affect expression of 2OST. 2OST is a sulfotransferase responsible for sulfation of the heparan sugar chain . Previous unpublished research by our lab has made evident 2OST?s essential role in the progression of prostate cancer. My lab noted a four -fold increase in the transcription of 2OST between benign LNCAP cells and highly metastatic C42B cells; knocking out 2OST made cells less metastatic. Furthermore, the research noted increased transcription of 2OST when the cell encountered hypoxic conditions. As prostate cancer progresses dividing epithelial cells form a solid tumor, leaving the cells in the innermost region of the tumor with a lack of oxygen and nutrients. HIF1a is a transcription factor induced in response to a lack of oxygen. We have shown that in conjunction with its heterodimer HIF1b,that HIF1abinds to the 2OST promoter and turns on transcription of 2OST. This suggests that 2OST is turned on in response to hypoxic stress. ROS are a type of oxidative stress that we hypothesize will induce a similar 2OST response. Functioning on the assumption that the cell will react similarly to an equally stressful condition, I am investigating the effect of ROS induced transcription factors on 2OST. Since 2OST is essential for the progression of prostate cancer, it is now key to understand the factors which contribute to its over expression. This understanding will help halt the progression of the disease as well as similar cancers.