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Monitoring daunorubicin‐induced alterations in protein expression in pancreas carcinoma cells by two‐dimensional gel electrophoresis
Author(s) -
Möller Anja,
Malerczyk Claudius,
Völker Uwe,
Stöppler Hubert,
Maser Edmund
Publication year - 2002
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/1615-9861(200206)2:6<697::aid-prot697>3.0.co;2-f
Subject(s) - daunorubicin , dna damage , biology , transactivation , cancer research , pancreas , apoptosis , cancer cell , cell growth , cancer , chemotherapy , gene expression , endocrinology , dna , biochemistry , genetics , gene
Tumors of the pancreas are characterized by a high intrinsic potency to develop chemoresistance towards cytotoxic drugs, which is the main cause of ineffective treatment. The phenomenon of multidrug resistance is known to be a multifactorial event in which several mechanisms act simultaneously. We investigated the response of pancreas tumor cells after exposure to the anthracycline daunorubicin (DRC), a well‐known antitumor agent in chemotherapy, by two‐dimensional gel electrophoresis (2‐DE). DRC is known to cause DNA damage and to affect tumor cell growth. Importantly, we aimed at investigating alterations in the protein expression pattern after first contact of the tumor cells with DRC, thus simulating a situation close to clinical chemotherapy and elucidating cell survival strategies following initial drug exposure. A concentration dependent up‐regulation of a variety of proteins was observed, indicating that cell response to DRC involves multiple signaling events. Since the p53 tumor suppressor is essentially involved in the regulation of cell growth and controlled cell death (apoptosis) after cellular stress (like DNA damage), we investigated the role of p53 in DRC‐resistant and ‐sensitive pancreas carcinoma cells by measuring p53 transcriptional transactivation activities. No differences in p53 activities were observed in response to DRC treatment in both pancreas cell lines, whereas mamma carcinoma cells (MCF‐7), possessing wild‐type p53, demonstrated the expected increase in p53 transcriptional transactivation activity. Hence, the tested pancreas carcinoma cells harbor a mutant, nonfunctional p53. We additionally analyzed the steady state protein levels of the cyclin dependent kinase inhibitor p21 CIP1 , which is known to be involved in cell cycle control. Interestingly, p21 CIP1 was induced by DRC in sensitive cells in a concentration dependent manner and was highest in resistant cells. In conclusion, our results suggest that the induction of proteins by DRC in pancreas carcinoma cells, as observed by 2‐DE, occurs independently from p53 signaling events, but is probably associated with increased levels of p21 CIP1 .