| Co-Investigator(Kenkyū-buntansha) |
HIRATA Masato Kyushu University, Faculty of Dental Science, Professor, 大学院・歯学研究院, 教授 (60136471)
KANEMATSU Takashi Kyushu University, Faculty of Dental Science, Associate Professor, 大学院・歯学研究院, 助教授 (10264053)
|
|---|
| Research Abstract |
The protein PRIP (two isotypes, type 1 and 2) was first isolated from rat brain as an inositol 1,4,5-trisphosphate-binding protein with a domain organization similar to that of phospholipase C (PLC)-δ1, but lacking PLC activity. The gene encoding PRIP-1 resides in 2q33, which is deleted in many cell types of lung carcinoma, indicating that PRIP, especially its type 1 is the product of tumor-suppressor gene. To elucidate the possible involvement of PRIP in anti-tumor activities, we here examined as follows :
(1)HeLa cells which lacks an intrinsic PRIP, were transformed to those expressing PRIP controlled by the usage of mifepristone by the transfection of PRIP gene attached to mifepristone-sensitive gene. These cells were measured for the rate of proliferation by counting cell number during the cultivation period, and it was found that there was little change in the rate between the mutant and control HeLa cells.
(2)Skin fibroblasts were prepared from PRIP-1 and -2 double knock-out mice a
… More
nd control mice, followed by the cultivation to measure the cell proliferation rate. There was little difference in the proliferation, indicating that PRIP might not be involved in the processes for cell proliferation.
(3)Activation of Akt is implicated in cell survival pathway, which is inhibited by inositol hexakisphosphate (InsP_6), thus causing cell death by apoptosis. In the previous research, we elucidated that InsP_6 inhibited the activation of Akt and following processes including the activation of IκB kinase and NFκB, but did not inhibit phosphoinositide 3-kinase activity, indicating that InsP_6 might compete with phosphatidylinositol 3,4,5-trisphosphate for the activation of phosphoinositide- dependent kinase. Therefore, it might be assumed that PRIP binding inositol phosphates and phosphoinositides, exhibits some effect on these processes, however, PRIP transfected into HeLa cells showed little effects.
Together, these results suggest that PRIP is not directly implicated in the processes for cell proliferation and cell survival. Less
|
