The action of Pdcd4 may be cell type specific: evidence that reduction of dUTPase levels might contribute to its tumor suppressor activity in Bon-1 cells.
Pdcd4 (programmed cell death protein 4) was identified as a gene up-regulated during apoptosis and, additionally, seems to have a function as a tumor suppressor. However, there are conflicting data concerning its role in programmed cell death and most results for its action as an inhibitor for neoplastic transformation are derived from experiments with epidermal cells. Therefore, we were interested to investigate if the action of Pdcd4 might be cell type specific. For that purpose we examined the expression of Pdcd4 and several other proteins in various tumor cell lines. We could not find any correlation of Pdcd4 levels and expression of proteins associated with cell cycle and/or apoptosis in different cell lines. Furthermore, we stably transfected two cell lines (Bon-1 and HCT116) to over-express Pdcd4 and analyzed protein expression. Although we found several regulated proteins none of these proteins were affected in both cell lines in the same manner. For instance, dUTPase expression was reduced in Bon-1 cells but not changed in HCT116 cells. This regulation might be important for the sensitivity of cells to anti-cancer drugs like inhibitors of thymidilate synthase. Therefore, we conclude that the function of Pdcd4 might be cell type specific. A role for Pdcd4 in apoptosis or as a tumor suppressor might be limited to certain cell types.
Lankat-Buttgereit
Brigitte
B
Clinical Research Unit for Gastrointestinal Endocrinology, University Hospital of Giessen and Marburg, Baldingerstrasse, Marburg, Germany. lankatbu@staff.uni-marburg.de
Lenschen
Barbara
B
Schmidt
Harald
H
Göke
Rüdiger
R
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D011755:Pyrophosphatases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014162:Transfection
D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase; D005472:Fluorouracil