Pancreatic cancer is the fourth leading cause of cancer death in the United States with a low 5-year survival rate of 7%, mainly due to late diagnosis. KRas is a signaling enzyme, that is mutated and, in turn, activated in most pancreatic cancer cases. HuR is a ribonucleic acid (RNA)-binding protein that has been seen to be upregulated in pancreatic cancer and is pro-tumorigenic. HuR gets cleaved into CP1, which binds differently than HuR and plays a role in a cells apoptosis, which is usually anti-tumorigenic. The relationship between these three: KRas, HuR, and CP1 are being investigated by seeing how the activity of KRas affects levels of HuR and CP1 in pancreatic ductal adenocarcinoma (PDAC) cells. To do this, western blots were done to look at the levels of HuR and CP1 in different PDAC lines with mutated and knocked down KRas. Different stressors, typical of the tumor environment, were invesigated in terms of their effect on HuR and CP1 in combination with KRas. The first stressor to be used was depleted serum and its effect on HuR and CP1 on different cancerous and non-cancerous pancreatic ductal cells was studied. Gemcitabine was then used as a stressor, as it is most commonly used in chemotherapy for pancreatic cancer. With these various stressors being tested, we can see if HuR and CP1 are being upregulated by the different stressors, by KRas, or by both, and how this is affecting the spread of the cancer. When PDAC’s with mutated consitutively active KRas were stressed by serum starvation, the HuR and CP1 levels increased. BxPC3, which is a PDAC with wild-type KRas, when serum starved, had decreased levels of HuR. Also, when KRas was knocked down, it increased CP1 levels.

How HuR and CP1 are affected by KRas and stressors in pancreatic cancer cells

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.