Targeting transcription factor NFkappaB: comparative analysis of proteasome and IKK inhibitors.

Nuclear factorkappaB (NFkappaB) plays a critical role in cancer development and progression. Thus, the NFkappaB signaling pathway provides important targets for cancer chemoprevention and anticancer chemotherapy. The central steps in NFkappaB activation are phosphorylation and proteasome-dependent degradation of its inhibitory proteins termed IkappaBs.

Epithelial cells in the hair follicle bulge do not contribute to epidermal regeneration after glucocorticoid-induced cutaneous atrophy.

One of the major adverse effects of glucocorticoid therapy is cutaneous atrophy, often followed by the development of resistance to steroids. It is accepted that epithelial stem cells (SCs) located in the hair follicle bulge divide during times of epidermal proliferative need. We determined whether follicular epithelial SCs and their transit amplifying progeny were stimulated to proliferate in response to the chronic application of glucocorticoid fluocinolone acetonide (FA).

The mechanisms of tumor suppressor effect of glucocorticoid receptor in skin.

Glucocorticoid hormones exert a tumor suppressor effect in different experimental models, including mouse skin carcinogenesis. The glucocorticoid control of cellular functions is mediated via the glucocorticoid receptor (GR), a well-known transcription factor that regulates genes by DNA-binding dependent transactivation, and DNA-binding independent transrepression through negative interaction with other transcription factors. In this perspective, we analyze known mechanisms that underlie the anticancer effect of GR signaling, including effects on cell growth, differentiation, apoptosis, and angiogenesis.

The tumor suppressor effect of the glucocorticoid receptor in skin is mediated via its effect on follicular epithelial stem cells.

Glucocorticoids are potent inhibitors of mouse skin tumorigenesis. The glucocorticoid control of cellular functions is mediated via the glucocorticoid receptor (GR), a well-known transcription factor. Recently, we generated transgenic mice overexpressing GR under control of the keratin5 (K5) promoter, and showed that K5.

Tumor suppressor activity of glucocorticoid receptor in the prostate.

Glucocorticoids are extensively used in combination chemotherapy of advanced prostate cancer (PC). Little is known, however, about the status of the glucocorticoid receptor (GR) in PC. We evaluated over 200 prostate samples and determined that GR expression was strongly decreased or absent in 70-85% of PC.