کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1928715 | 1050418 | 2013 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Differential regulation of cyclin-dependent kinase inhibitors in neuroblastoma cells Differential regulation of cyclin-dependent kinase inhibitors in neuroblastoma cells](/preview/png/1928715.png)
• GRP-R signaling differentially regulated the expression of p21 and p27.
• Silencing GRP/GRP-R downregulated p21, while p27 expression was upregulated.
• Inhibition of GRP/GRP-R signaling enhanced PTEN expression, correlative to the increased expression of p27.
• PTEN and p27 co-localized in cytoplasm and silencing PTEN decreased p27 expression.
Gastrin-releasing peptide (GRP) and its receptor (GRP-R) are highly expressed in undifferentiated neuroblastoma, and they play critical roles in oncogenesis. We previously reported that GRP activates the PI3K/AKT signaling pathway to promote DNA synthesis and cell cycle progression in neuroblastoma cells. Conversely, GRP-R silencing induces cell cycle arrest. Here, we speculated that GRP/GRP-R signaling induces neuroblastoma cell proliferation via regulation of cyclin-dependent kinase (CDK) inhibitors. Surprisingly, we found that GRP/GRP-R differentially induced expressions of p21 and p27. Silencing GRP/GRP-R decreased p21, but it increased p27 expressions in neuroblastoma cells. Furthermore, we found that the intracellular localization of p21 and p27 in the nuclear and cytoplasmic compartments, respectively. In addition, we found that GRP/GRP-R silencing increased the expression and accumulation of PTEN in the cytoplasm of neuroblastoma cells where it co-localized with p27, thus suggesting that p27 promotes the function of PTEN as a tumor suppressor by stabilizing PTEN in the cytoplasm. GRP/GRP-R regulation of CDK inhibitors and tumor suppressor PTEN may be critical for tumoriogenesis of neuroblastoma.
Journal: Biochemical and Biophysical Research Communications - Volume 435, Issue 2, 31 May 2013, Pages 295–299