Induction of mitogenic signalling in the 1LN prostate cell line on exposure to submicromolar concentrations of cadmium+.
Journal Article (Journal Article)
Cadmium exposure increases the risk of prostate cancer. We now describe the effects of Cd2+ on signalling and proliferation in 1LN prostate cells. Cd2+ increased [3H]thymidine uptake and cell number twofold. Cd2+ elevated intracellular IP3, cytosolic-free Ca2+, phosphorylated MEK1/2, ERK1/2, p38 MAPK and JNK two- to threefold. Increased PDK1 and phosphorylation of the 85-kDa regulatory subunit of PI 3-kinase, Akt and p70s6k were also observed. Cd2+ treatment increased transcription factors NFkappaB and CREB, and the expression of c-fos and c-myc. Cd2+-induced increased uptake of [3H]thymidine was abolished by translational and transcriptional inhibitors, and Ca2+ channel blockers. Inhibition of phospholipase C and of Ca2+ binding to IP3 receptors inhibited Cd2+-induced DNA synthesis as did inhibition of tyrosine kinases, protein kinase C, PI 3-kinase, farnesyl transferase, MEK1/2, ERK1/2 and p38MAPK. Thus signalling events, which are triggered on exposure of 1LN cells to submicromolar concentrations of Cd2+, induce increased proliferation of these cells.
Full Text
Duke Authors
Cited Authors
- Misra, UK; Gawdi, G; Pizzo, SV
Published Date
- November 2003
Published In
Volume / Issue
- 15 / 11
Start / End Page
- 1059 - 1070
PubMed ID
- 14499349
International Standard Serial Number (ISSN)
- 0898-6568
Digital Object Identifier (DOI)
- 10.1016/s0898-6568(03)00117-7
Language
- eng
Conference Location
- England