Dynamic distribution of ERK,p38 and JNK during the development of pancreatic ductal adenocarcinoma |
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| Affiliation: | 1. Department of Molecular Cell Biology, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel;2. Department of Veterinary Resources, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel;3. Wolfson Hospital, Holon 58100, Israel;4. Department of Gastroentrology, Kaplan Medical Center, Rehovot 76100, Israel;5. Department of Biological Regulation, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel;1. Division of Anatomy, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania;2. MEDCENTER, Center of Excellence in Laboratory Medicine and Pathology, Bucharest, Romania;3. International Society of Regenerative Medicine and Surgery (ISRMS), Romania;4. Department of Medicine and Surgery, University of Catania, Italy;5. Division of Ophthalmology, S.C.U.O., Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania;6. Clinical Hospital of Ophthalmologic Emergencies (S.C.U.O.), Bucharest, Romania;1. Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy;2. Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy;1. Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China;2. College of Life Science, Dalian Nationalities University, Dalian 116600, China;3. Environment and Resources College Dalian Nationalities University, Dalian 116600, China;1. Department of Brain Physiology, State Key Laboratory of Molecular and Cellular Biology, Bogomoletz Institute of Physiology, National Academy of Sciences, Bogomoletz Str. 4, Kiev 01024, Ukraine;2. Laboratory of Experimental Neurophysiology, Pirogov National Medical University, Ministry of Public Health of Ukraine, Pirogov Str. 56, Vinnitsa 21018, Ukraine;3. Department of Movement Physiology, Bogomoletz Institute of Physiology, National Academy of Sciences, Bogomoletz Str. 4, Kiev 01024, Ukraine;1. Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada;2. Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 2V4, Canada |
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| Abstract: | We recently discovered that oncogenic c-kit is highly expressed concomitantly with the development of pancreatic ductal adenocarcinoma (PDAC). Since oncogenic c-kit may activate major pathways of protein tyrosine phosphorylation, we decided to investigate this issue in the major protein phosphorylation cascades. In normal pancreas labeling with antiphosphorylated ERK1/2 (pERK1/2) antibody was mainly confined to islets of Langerhans in close overlapping with insulin containing cells. Phosphorylated p38 (pp38) showed a similar pattern of distribution, while only weak labeling was evident for pJNK and no labeling of pMEK was observed. As expected, general ERK1/2 (gERK1/2), general p38 (gp38), general JNK (gJNK) as well as general MEK (gMEK) were all evident in islets of Langerhans and in the exocrine tissue. In early development of PDAC, pERK1/2 and pp38 retained their localization in islets of Langerhans. Intensive staining of pERK1/2 was also evident in the cancerous ducts, while the labeling with antibodies to pp38 was more moderate. While pJNK staining in islets of Langerhans was weak, with no labeling in the cancerous ducts, antibodies to gJNK revealed intensive staining suggesting the weak staining of pJNK is not due to the lack of the enzyme. In a more advanced stage of PDAC the carcinomas were clearly stained with pERK1/2 and pp38, while moderate staining with pJNK was also evident. In liver metastases, the cancer cells were heavily labeled with all three phospho-MAPKs. It should be noted that the localization of all three kinases was mainly in the cell nuclei. In the more advanced stage of PDAC, heavy labeling was evident using antibodies to gERK1/2, gp38, gJNK and gMEK. However, no labeling to pMEK was evident in parallel sections. Our data suggest that both in normal and cancerous pancreas, most of the MAPK activities are located in islets of Langerhans and cancerous ducts. It is suggested that using inhibitors to protein kinases may attenuate the progression of the disease. |
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| Keywords: | PDAC ERK1/2 p38 JNK Islets of Langerhans β cells PDAC" },{" #name" :" keyword" ," $" :{" id" :" kw0040" }," $$" :[{" #name" :" text" ," _" :" pancreatic ductal adenocarcinoma pERK1/2" },{" #name" :" keyword" ," $" :{" id" :" kw0050" }," $$" :[{" #name" :" text" ," _" :" phosphorylated ERK1/2 pp38" },{" #name" :" keyword" ," $" :{" id" :" kw0060" }," $$" :[{" #name" :" text" ," _" :" phosphorylated p38 pJNK" },{" #name" :" keyword" ," $" :{" id" :" kw0070" }," $$" :[{" #name" :" text" ," _" :" phosphorylated JNK pMEK" },{" #name" :" keyword" ," $" :{" id" :" kw0080" }," $$" :[{" #name" :" text" ," _" :" phosphorylated MEK gERK1/2" },{" #name" :" keyword" ," $" :{" id" :" kw0090" }," $$" :[{" #name" :" text" ," _" :" non-phosphorylated ERK1/2 gp38" },{" #name" :" keyword" ," $" :{" id" :" kw0100" }," $$" :[{" #name" :" text" ," _" :" non-phosphorylated p38 gJNK" },{" #name" :" keyword" ," $" :{" id" :" kw0110" }," $$" :[{" #name" :" text" ," _" :" non-phosphorylated JNK gMEK" },{" #name" :" keyword" ," $" :{" id" :" kw0120" }," $$" :[{" #name" :" text" ," _" :" non-phosphorylated MEK MAPK" },{" #name" :" keyword" ," $" :{" id" :" kw0130" }," $$" :[{" #name" :" text" ," _" :" mitogen-activated protein kinase |
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