ИСТИНА

Pancreatic carcinoma is one of the most aggressive human neoplasms having extremely poor prognosis with a median survival of 4-6 months. Even after surgical intervention with a curative intention, the five-year survival rate is in specialized centres at best 15% without and 25% with adjuvant therapy. Recently, we have shown that the key photoreceptor proteins, that are normally restricted to retinal cells and the pineal gland, function in lung cancer and melanoma cells as cancer-retina antigens (CRA). The following photoreceptor proteins were classified as CRA: rhodopsin, transducin (Tr), cGMP-phosphodiesterase (PDE6), cGMP-dependent channels, guanylyl cyclase 1 (GC1), rhodopsin kinase, recoverin, and arrestin. The main aim of the present work was to investigate the phenomenon of the aberrant CRA expression in pancreatic carcinoma cells with a focus on function of GC1 in the tumor cells. In this work, we showed that CRA are expressed in pancreatic carcinoma cell lines and tumors. Moreover, the CRA, GC1, PDE6 and Tr are expressed in pancreatic cancer at a high frequency. The aberrant expression of CRA leads to autoantibody production in the patients with pancreatic cancer. Also, we found that GC1 is functional in pancreatic carcinoma cell lines, and this enzyme is involved in cGMP metabolism and Ca2+ accumulation in the cell lines. Knock-down of GC1 leads to decrease of the viability, proliferation and migration capacity of pancreatic carcinoma cell lines, but does not affect the spontaneous apoptosis of the cells. Besides, the GC1 knock-down of reduces the tumor volume, appearance of peritoneal carcinosis and metastases, and has a tendency to prolong a survival of the tumor-bearing mice in an orthotopic model of pancreatic cancer. We suggest that the aberrant expression of GC1 in pancreatic carcinoma cells could be important for the tumor survival. Establishing of new methods for an in vivo knock-down of GC1 might be important for the pancreatic carcinoma treatment.