FDE related signal gene therapy especially melanoma

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 16390585
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Mie University
• Principal Investigator: TAGAWA Toshiro Mie University, Graduate School Of Medicine, Oral and Maxillofacial Surgery, Professor (30046346)
• Co-Investigator(Kenkyū-buntansha): INUI Madoka Mie University, Graduate School Of Medicine, Oral and Maxillofacial Surgery, Associate Professor (70159961) ; MURATA Taku Mie University, Hospital, Oral and Maxillofacial Surgery, Assistant Professor (80242965)
• Project Period (FY): 2004 – 2006
• Keywords: phosphodiesterase / melanoma / gene therapy

Research Abstract

cAMP and cGMP are critical intracellular second messengers that mediate biological responses initiated by diverse extracellular signals. By catalyzing hydrolysis of cyclic nucleotides, phosphodiesterases (PDEs) regulate intracellular concentrations and effects of these second messengers. At least 11 PDE gene families of these enzymes have been identified. Some PDE isoforms are selectively expressed in various normal cells. However, there are a few reports as to expression and function of PDEs in malignant tumor cells. So, we studied the expression and function of PDEs in malignant tumor cells, especially malignant melanoma cells.
Four human oral malignant melanoma cell line (HMG, PMP, MMN9 and MAA), human vaginal malignant melanoma cell line (MVH-II), two human skin malignant melanoma cell line (G361 and C32), human lymph-node metastatic malignant melanoma cell line (WM-266-4), and human liver adenocarcinoma cell line (SK-Hep-1) were used in this study. Each cell line expressed some PDEs. HMG cells expressed PDE3A, PDE3B, PDE4B, PDE4D and PDE7A. PDE4 specific inhibitors stimulated the cell growth, but PDE3 and PDE7 specific inhibitors did not changed the cell growth. PMP cells highly expressed PDE2, and PDE2 specific inhibitor and PDE2 siRNA inhibited the cell growth and invasion. There was no mutation in PDE genes in these cells. By baculovirus expression vector system, recombinant PDEs were expressed in Sf9 cells. From these data, PDE signals are very important in malignant melanoma cells, and maybe gene therapies for PDE related signal are effective.