Download - FBW7/CDC4 and Endometrial Cancer
FBW7/CDC4 and Endometrial Cancer
Michael Mastropole
Overview
• FBW7/CDC4 is a family of genes• Tumor suppressor• Directly binds to cyclin E• Mutated in about 16% of endometrial cancers
Ubiquitylation
http://upload.wikimedia.org/wikipedia/commons/7/7f/Ubiquitylation.png
The SCF Complex (E3 ligase)
Wang et al. 2012
CDC4 targets Cyclin E for Proteolysis
Strohmaier et al. 2001
http://eweb.furman.edu/~wworthen/bio111/4cyclins.jpg
Cyclin E is required for G1/S Transition
Mouse Model
Wang et al. 2012
Endometrial Cancer
• Endometrium- lining of the uterus
• Typically occurs within a few decades of menopause
• 49,560 new cases in 2013
hCDC4 mutations
Spruck et al. 2002
Treatments
• Surgery– Hysterectomy along with removal of ovaries,
fallopian tubes, and lymph nodes– Helps stage the cancer
• Chemotherapy– Taxol
• Radiation• Potential Treatments– Cdk2 inhibitors
www.cancer.org
Prognosis
• 1 year survival rate– 92%
• 5 year survival rate if cancer has not spread– 95%
• 5 year survival rate if cancer has spread– 23%
www.nlm.nih.gov
References
• http://www.nature.com/nature/journal/v413/n6853/full/413316a0.html
• http://cancerres.aacrjournals.org/content/62/16/4535.long
• http://www.cancer.org/cancer/endometrialcancer/detailedguide/endometrial-uterine-cancer-treating-by-stage
• http://www.nlm.nih.gov/medlineplus/ency/article/000910.htm
• http://www.sciencedirect.com/science/article/pii/S0014579312002049