BMP receptor1a Amit Patel
BMP receptor1a Amit Patel. 2005 Estimated US Cancer Deaths* ONS=Other nervous system. Source: American Cancer Society, 2005. Men 295,280 Women 275,000.
Dec 21, 2015
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BMP receptor1aAmit Patel
2005 Estimated US Cancer Deaths*
ONS=Other nervous system.Source: American Cancer Society, 2005.
Men295,280
Women275,000
27% Lung & bronchus
15% Breast
10% Colon & rectum
6% Ovary
6% Pancreas
4% Leukemia
3% Non-Hodgkin lymphoma
3% Uterine corpus
2% Multiple myeloma
2% Brain/ONS
22% All other sites
Lung and bronchus 31%
Prostate 10%
Colon & rectum 10%
Pancreas 5%
Leukemia 4%
Esophagus 4%
Liver and intrahepatic 3%bile duct
Non-Hodgkin 3% Lymphoma
Urinary bladder 3%
Kidney 3%
All other sites 24%
Colon Cancer is an Important Cause of Cancer Deaths in the US
Causes of Colon Cancer
Source: National Institute of Gastroenterology.
Juvenile Polyposis
Source: Mount Sinai Hospital
Which Gene Causes JP?
A heterogeneous disease– 15%-20% of mutations occur on SMAD4– 25-40% of mutations occur on BMPR1a– Remaining causes are unknown
The BMP/TGF-ß Family
Waite and Eng, Nature Reviews 4:763-773 (2003)
BMPR1a is a BMP receptor
Waite and Eng, Nature Reviews 4:763-773 (2003)
Loss of BMPR1a leads to embryonic lethality
Mishina et al, Genes & Development 9:3027-3027 (1995)
BMPR1a signaling is important inmany cell fates decisions in embryonic &
postembryonic development!
Wild Type
Mutant
Mishina et al, Genes & Development 9:3027-3027 (1995)
E 7.0 E 8.5
Heart -specific deletion of BMPR1a leads to cardiac anomalies
Juvenile Polyposis
Source: Mount Sinai Hospital
What Goes Wrong in Juvenile Polyposis?
Waite and Eng, Nature Reviews 4:763-773 (2003)
How Do These Mutations Lead to Cancer?
How Do These Mutations Lead to Cancer?
Used mice as a model organism
How Do These Mutations Lead to Cancer?
BMPR1a is expressed in all but the proliferating cells
He et al, Nature Genetics 36: 1117-1121 (2004)
How Do These Mutations Lead to Cancer?
-Inactivating BMPR1a in developing colontriggered the formation of polyps
He et al, Nature Genetics 36: 1117-1121 (2004)
Wnt Expression
WNT
He et al, Nature Genetics 36: 1117-1121 (2004)
Inactivating BMPR1a in developing colon triggered the formation of
polyps
Crosnier et al, Nature Genetics 7: 349-359 (2006)
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