Programmed cell death protein 4 (PDCD4) acts as a tumor suppressor in neuroendocrine tumor cells.

PDCD4 is a new tumor suppressor gene. In the current study, we show that overexpression of PDCD4 in carcinoid cells results in inhibition of cell proliferation. This is most likely caused by a PDCD4-induced downregulation of carbonic anhydrase type II which catalyzes the production of bicarbonate, a fundamental substrate for many cellular pathways.

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.

Bisphenol A diglycidyl ether-induced apoptosis involves Bax/Bid-dependent mitochondrial release of apoptosis-inducing factor (AIF), cytochrome c and Smac/DIABLO.

(1) Bisphenol A diglycidyl ether (BADGE) is a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) antagonist, which is able to induce apoptosis in tumor cells independently of PPAR-gamma in caspase-dependent and -independent manners. Additionally, BADGE promotes TRAIL-induced apoptosis. (2) We report that BADGE activates via Bax and caspases-2 and -8 both the intrinsic and extrinsic apoptotic pathways using Bid as a shunt.

DNA repair protein MGMT protects against N-methyl-N-nitrosourea-induced conversion of benign into malignant tumors.

Tumor formation is a multi-step process that can be divided into the stages of tumor initiation, promotion and progression. Previously, we showed that overexpression in skin of mice of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) protects against N-methyl-N-nitrosourea (MNU)-induced tumor initiation without affecting tumor promotion. This indicated that O(6)-methylguanine, which is specifically repaired by MGMT, is a major tumor-initiating lesion.

Transgenic systems in studies on genotoxicity of alkylating agents: critical lesions, thresholds and defense mechanisms.

Transgenic systems, both cell lines and mice with gain or loss of function, are being used in order to modulate the expression of DNA repair proteins, thus allowing to assess their contribution to the defense against genotoxic mutagens and carcinogens. In this review, questions have been addressed concerning the use of transgenic systems in elucidating critical primary DNA lesions, their conversion into genotoxic endpoints, low-dose effects, and the relative contribution of individual cellular functions in defense. It has been shown that the repair protein alkyltransferase (MGMT) is decisive for protection against methylating and chloroethylating compounds.