Clinical-liver,pancreas, and biliary tractDown-regulation of the dual-specificity phosphatase MKP-1 suppresses tumorigenicity of pancreatic cancer cells☆
Section snippets
Tissue samples
Normal human pancreatic tissue samples (13 male, 7 female donors; median age 42 years; range 14–73 years), chronic pancreatitis tissues (18 male, 2 female; median age 47 years; range 30–60 years), and pancreatic cancer tissues (13 male, 8 female; median age 64 years; range 48–83 years) were obtained through an organ donor program and from surgical specimens obtained from patients with severe symptomatic chronic pancreatitis or from pancreatic cancer patients. According to the TNM classification
Mitogen-activated protein kinase phosphatase-1 expression in human pancreatic cancer and chronic pancreatitis
We first examined the expression levels of MKP-1 messenger RNA (mRNA) in pancreatic cancer specimens and normal pancreatic tissues. Northern blot analysis of total RNA isolated from 21 cancerous and 20 normal pancreatic tissues revealed the presence of the 2.4-kb MKP-1 transcript7 at relatively low levels in 7 of 20 (35%) normal pancreatic samples. In the remaining samples the MKP-1 transcript was detectable only on the original autoradiographs. In contrast, in 12 of 21 (57%) pancreatic cancer
Discussion
MAPKs, which include the extracellular signal-regulated kinases (p42 and p44-MAPK), the c-Jun N-terminal kinases (JNK/SAPK), and p38-MAPK, play a pivotal role in cell proliferation and differentiation.3 Their function can be modulated by reversible phosphorylation. MAPKs are activated through complex phosphorylation cascades, in which a series of phosphorylation events occur by Raf (MAPKKK) and MEK (MAPKK),4 and their activation in turn leads to the phosphorylation and activation of a variety
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Supported in part by USPHS grant CA-40162 awarded by the National Cancer Institute (to M.K.).
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Q.L., J.G., and J.K. contributed equally to this work.