Pdcd4 inhibits growth of tumor cells by suppression of carbonic anhydrase type II.
To identify new genes that are upregulated during apoptosis we previously cloned rat pdcd4. While the role of pdcd4 is still unclear it seems to possess a tumor suppressor activity. Pdcd4 directly interacts with the RNA helicase eIF4A and inhibits protein synthesis by interfering with the assembly of the cap-dependent translation initiation complex. In the present study, we show that pdcd4 suppresses carbonic anhydrase type II protein expression in HEK293 and Bon-1 carcinoid cells. Since tumor cells require a high bicarbonate flux for their growth, carbonic anhydrase suppression results in growth inhibition. Similar to pdcd4, carbonic anhydrase inhibitor ethoxyzolamide reduces growth of several endocrine tumor cell lines. Thus, the translation inhibitor pdcd4 represses endocrine tumor cell growth by suppression of carbonic anhydase II. Furthermore, carbonic anhydrase inhibitors might represent promising tools for anti-endocrine tumor treatment.
Lankat-Buttgereit
B
B
Clinical Research Unit for Gastrointestinal Endocrinology, University of Marburg, Baldingerstrasse, 35033 Marburg, Germany.
Gregel
C
C
Knolle
A
A
Hasilik
A
A
Arnold
R
R
Göke
R
R
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors*; D002455:Cell Division; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004701:Endocrine Gland Neoplasms / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005016:Ethoxzolamide / Q000494:pharmacology; D006801:Humans; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D024402:Carbonic Anhydrase II; D005016:Ethoxzolamide