Abstract
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.
MeSH terms
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3-Phosphoinositide-Dependent Protein Kinases
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Bacterial Proteins*
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Cadmium / metabolism*
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Cell Division / physiology
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Cell Transformation, Neoplastic / metabolism*
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Cells, Cultured
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Enterotoxins / metabolism
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Humans
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JNK Mitogen-Activated Protein Kinases*
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MAP Kinase Kinase 4
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MAP Kinase Signaling System / physiology*
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Male
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / metabolism*
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NF-kappa B / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Prostate / cytology
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Prostate / enzymology*
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Protein Serine-Threonine Kinases / metabolism
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Protein Subunits
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Ribosomal Protein S6 Kinases, 70-kDa / metabolism
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Signal Transduction / physiology*
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Thymidylate Synthase / metabolism
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Type C Phospholipases / metabolism
Substances
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Bacterial Proteins
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Enterotoxins
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NF-kappa B
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Protein Subunits
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cytolytic enterotoxin protein, Aeromonas
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Cadmium
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Thymidylate Synthase
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3-Phosphoinositide-Dependent Protein Kinases
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PDPK1 protein, human
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Protein Serine-Threonine Kinases
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Ribosomal Protein S6 Kinases, 70-kDa
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases
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Type C Phospholipases