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BMP Receptor 1A Juvenile Polyposis

BMP Receptor 1A Juvenile Polyposis. Dayna Neo 3/21/13 Biol 445 001. Juvenile Polyposis is a rare autosomal dominant syndrome that increases your risk of intestinal tract cancer. Humpath.com. Juvenile Polyposis Daniel Calva , MD and James Howe, MD.

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BMP Receptor 1A Juvenile Polyposis

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  1. BMP Receptor 1A Juvenile Polyposis Dayna Neo 3/21/13 Biol 445 001

  2. Juvenile Polyposis is a rare autosomal dominant syndrome that increases your risk of intestinal tract cancer Humpath.com Juvenile Polyposis Daniel Calva, MD and James Howe, MD.

  3. BMPR1A is a receptor serine/threonine kinase that phosphorylates SMAD transcription factors Hardwick, James C et al

  4. BMPR1A is a tumor suppressor!!!!

  5. BMP pathway inhibits proliferation by inhibiting the Wntpathway BMP Pathway Wnt PTEN COX-2 expression Cell Proliferation EGF receptor

  6. Two-hit hypothesis and loss of heterozygosity leads to Juvenile Polyposis • Deletions, insertions, and missense/nonsense mutations  abnormally short, nonfunctional protein • No mutations observed in transmembranedomain • >90% penetrance Jyh-Cherng Yu and Chen Yang Shen

  7. Individuals with juvenile polyposis have mutations in their BMPR1A D E S B James R. Howe et. al

  8. Individual 12 will get JP E D B S Arrows represent bands corresponding to BMP1A mutations James R. Howe et. al

  9. BMPR1A is present at the base of each intestinal crypt Villus Crypt Hardwick, James C et al

  10. BMPR1A -/- lack the mesoderm layer during gastrulation Mishina Y et al

  11. Treatments include polypectomy, prophylactic colectomy, and restorative proctocolectomy A subject of current investigation involves cycloxygenase inhibitors Cleavelandclinic.org

  12. References • Bessa, P.C et al, Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I(basic concepts). Journal of Tissue Engineering and Regenerative Medicine 2008:2:1-13 • Hardwick, James C et al, Bone morphogenic protein signaling in colorectal cancer. Nature Reviews: Cancer 2008: 8: 806-812 • Children’s Hospital Boston, 2009. • JR Howe, et. al, Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nature. 2001 • JR Howe, et.al, The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. J Med Genet 2004, 41:484-491 • Juvenile Polyposis : (SMAD4) Sequencing and Deletion/Duplication, (BMPR1A) Sequencing and Deletion/Duplication • Kurland JE, et al, Cyclooxygenase-2 expression in polyps from a patient with juvenile polyposis syndrome with mutant BMPR1A. J PediatrGastroenterolNutr. 2007, Mar;44(3):318-325 • Lodewijk AA Brosens et, al. Juvenile polyposis syndrome. World Journal of Gastroenterology. • Mishina, Y. et al, Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes, Dev. 1995. Genes & Development. • Tian, Qiang et al, Bridging the BMP and Wnt Pathways by PI3 Kinase/Akt and 14-3-3. Landes Bioscience. Cell Cycle 4:2 215-216: February 2005.

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