Glucocorticoid receptor functions as a potent suppressor of mouse skin carcinogenesis

Oncogene
Irina V BudunovaThomas J Slaga

Abstract

Glucocorticoids are effective inhibitors of epidermal proliferation and skin tumorigenesis. Glucocorticoids affect cellular functions via glucocorticoid receptor (GR), a well-known transcription factor. Recently, we generated skin-targeted transgenic mice overexpressing GR under control of the keratin5 promoter (K5-GR mice). To test the hypothesis that GR plays a role as a tumor suppressor in skin, we bred K5-GR transgenic mice with Tg.AC transgenic mice, which express v-Ha-ras oncogene in the skin, and compared the susceptibility of F1 offspring to TPA-induced skin carcinogenesis. GR overexpression in the epidermis dramatically inhibited skin tumor development. In K5-GR/ras+ double transgenic mice papillomas developed later and the average number of tumors per animal was 15% (in males) and 40% (in females) of the number seen in wild type (w.t./ras+) littermates. In addition, the papillomas in w.t./ras+ animals were eight to nine times larger. GR overexpression resulted in a decrease in keratinocyte proliferation combined with a modest increase in apoptosis and differentiation of keratinocytes in K5-GR/ras+ papillomas. Our data clearly indicate that interference of GR transgenic protein with nuclear factor kappa B (NF-kappaB) t...Continue Reading

References

Aug 1, 1988·Carcinogenesis·J DiGiovanniK J Chenicek
Apr 1, 1987·Environmental Health Perspectives·D S Miller
Apr 1, 1995·Carcinogenesis·A I Robles, C J Conti
Jan 1, 1997·Critical Reviews in Eukaryotic Gene Expression·B M Jehn, B A Osborne
Oct 23, 1997·The Journal of Clinical Investigation·F DelaunayS Okret
Oct 9, 1999·The Journal of Biological Chemistry·A NalcaV M Rangnekar
Dec 2, 1999·Genes & Development·A BauerH Beug
Dec 22, 1999·Oncogene·M Barkett, T D Gilmore
Apr 4, 2000·Molecular Carcinogenesis·P PérezJ L Jorcano
May 29, 2000·Molecular and Cellular Biology·N RadojaM Tomic-Canic
Jul 6, 2000·The Journal of Clinical Investigation·R J Morris
May 30, 2001·Molecular and Cellular Endocrinology·N Takuwa, Y Takuwa
Jan 23, 2002·Cell Death and Differentiation·C W Distelhorst
Nov 1, 1970·Bulletin of Environmental Contamination and Toxicology·A R Thompson

❮ Previous
Next ❯

Citations

Jan 22, 2013·Cellular and Molecular Life Sciences : CMLS·Xiao-Yong ManMin Zheng
May 12, 2004·Chest·Zbigniew WalaszekThomas J Slaga
Nov 13, 2013·The Journal of Investigative Dermatology·Wendy B Bollag, Carlos M Isales
Jun 13, 2013·The Journal of Investigative Dermatology·Víctor LatorrePaloma Pérez
Oct 27, 2009·Ageing Research Reviews·Stephen R Spindler
Jul 28, 2007·The Journal of Investigative Dermatology·Dmitry V ChebotaevIrina V Budunova
May 15, 2007·Experimental and Molecular Pathology·Kengo MurataMasashi Fukayama
Jun 1, 2007·Molecular Carcinogenesis·Dmitry ChebotaevIrina Budunova
Apr 12, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Stella LogothetiVassilis Zoumpourlis
Mar 3, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Eric AssenatJean Marc Pascussi
May 24, 2015·Molecular and Cellular Endocrinology·Lisa M SevillaPaloma Pérez
Jul 16, 2016·Stress : the International Journal on the Biology of Stress·Lubica HorvathovaBoris Mravec
Nov 25, 2016·American Journal of Physiology. Cell Physiology·Jessica A ChadwickJill A Rafael-Fortney
Nov 28, 2007·Endocrinology·Pilar BayoPaloma Pérez
Feb 28, 2004·The Journal of Nutrition·Prasong TanmahasamutNeil Sidell
Dec 15, 2020·Seminars in Cancer Biology·Joan Font-DíazAnnabel F Valledor

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis