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Pdcd4 inhibits growth of tumor cells by suppression of carbonic anhydrase type II

B Lankat-Buttgereit1, C Gregel, A Knolle

  • 1Clinical Research Unit for Gastrointestinal Endocrinology, University of Marburg, Baldingerstrasse, 35033 Marburg, Germany.

Molecular and Cellular Endocrinology
|April 6, 2004
PubMed

Insights

Programmed cell death 4 (pdcd4) suppresses endocrine tumor cell growth by inhibiting carbonic anhydrase II. Carbonic anhydrase inhibitors show promise for anti-endocrine tumor therapies.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Programmed cell death 4 (pdcd4) is a newly identified gene upregulated during apoptosis.
  • Pdcd4 exhibits tumor suppressor activity and interacts with eukaryotic initiation factor 4A (eIF4A) to inhibit protein synthesis.
  • Tumor cell proliferation relies on high bicarbonate flux, which is regulated by carbonic anhydrase.

Purpose of the Study:

  • To investigate the role of pdcd4 in regulating carbonic anhydrase II expression.
  • To determine the effect of pdcd4-mediated carbonic anhydrase suppression on endocrine tumor cell growth.
  • To evaluate the therapeutic potential of carbonic anhydrase inhibitors in endocrine tumors.

Main Methods:

  • Cloning of rat pdcd4.
  • Analysis of pdcd4's effect on carbonic anhydrase type II protein expression in HEK293 and Bon-1 carcinoid cells.
  • Assessment of ethoxyzolamide's effect on endocrine tumor cell line growth.

Main Results:

  • Pdcd4 was shown to suppress carbonic anhydrase type II protein expression in HEK293 and Bon-1 carcinoid cells.
  • Suppression of carbonic anhydrase by pdcd4 led to growth inhibition of these tumor cells.
  • The carbonic anhydrase inhibitor ethoxyzolamide demonstrated reduced growth in several endocrine tumor cell lines.

Conclusions:

  • The translation inhibitor pdcd4 represses endocrine tumor cell growth through the suppression of carbonic anhydrase II.
  • Carbonic anhydrase inhibitors may serve as a promising therapeutic strategy for endocrine tumors.

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