RET Proto- Oncogene in The Development of Thyroid Cancer: Multiple Endocrine Neoplasia Type 2

Please download to get full document.

View again

of 14
5 views
All materials on our website are shared by users. If you have any questions about copyright issues, please report us to resolve them. We are always happy to assist you.

Download

Document Related
Document Description
RET Proto- Oncogene in The Development of Thyroid Cancer: Multiple Endocrine Neoplasia Type 2. Courtney Brooks. Overview. MEN Type 2 RET Gene-Role in Normal Development Normal RET Signaling Pathway Mutations Responsible for MEN Type 2 Mutant RET Signaling Pathway
Document Share
Document Transcript
RET Proto- Oncogene in The Development of Thyroid Cancer: Multiple Endocrine Neoplasia Type 2Courtney BrooksOverview
  • MEN Type 2
  • RET Gene-Role in Normal Development
  • Normal RET Signaling Pathway
  • Mutations Responsible for MEN Type 2
  • Mutant RET Signaling Pathway
  • Diagnosis and Treatment for the Cancer
  • Multiple Endocrine Neoplasia Type 2
  • Thyroid Cancer
  • Germ line point mutations in RET gene.
  • Cause over activation of RET
  • Triggers proliferation in endocrine cells.
  • 3 Forms of MEN Type 2
  • MEN Type 2a
  • MEN Type 2b
  • FMTC
  • RET
  • Gene on chromosome 10 q 11.2
  • Encodes a receptor tyrosine kinase
  • Required for maturation of nervous system and kidney morphogenesis
  • RET: Role in Normal DevelopmentRET deficient mice :Die shortly after birthLack the Enteric Nervous SystemDisplay Renal Agenesis (no Kidney)Have Fewer Thyroid C CellsComponents of the RET Signaling Pathway
  • Co-receptors:
  • GFR  1,2, 3, & 4
  • Growth Factor Ligands:
  • GDNF, NRTN, ARTN, PSPNRETCysGFR  1Extracellular DomainGDNFCysCysCysCell MembranePIntracellular DomainPRAS-RAF PathwayPI3 Kinase PathwayRET Proto-Oncogene in MEN Type 2
  • Germline point mutations of RET are responsible for all Forms of MEN Type MEN 2
  • The mutations affect either the extracellular or the intracellular tyrosine kinase domain of RET receptor.
  • RET Gene Showing Mutations For MEN Type 2The Effects of Mutations on RET Function
  • Ligand independent dimerization, activation, and transformation.
  • Constitutive Phosphorylation of intracellular proteins.
  • Overactive Signaling
  • RETCysGFR  1CysExtracellular DomainArgCysCell MembranePPIntracellular DomainPPOver Active Signalling to CellsUncontrolled Cell ProliferationDiagnosis and Management of MEN Type 2
  • Genetic Screening for RET mutations
  • Thyrodectomy
  • New Therapeutic Strategies : Inhibitors specific for RET oncoproteins
  • Sources
  • Albert, L. Carniti, C. RET and NTRK1. 2003. Proto-Oncogenes in Human Diseases. Journal of Cellular Physiology. 195: 168-186
  • Manie, S. Santoro, M. 2001. The RET receptor: function in development and dysfunction in congenital malformation. Trends in Genetics. 17 (10): 580-589
  • MEN Syndromes. 2000. www.endocrineweb.com/men/men2.html
  • Borello, MG, Mercalli E. 1995. RET activation by germline MEN 2A, and MEN 2 B mutations. Oncogene 11:2419-2427
  • Mulligan LM, et al. Specific mutations of the RET proto-oncogene are related to MEN 2A and FMTC. Nat Genet. 1994; 6(1):70-4
  • Search Related
    Previous Slide

    6 February 2009

    Next Slide

    HDF5-iRODS

    We Need Your Support
    Thank you for visiting our website and your interest in our free products and services. We are nonprofit website to share and download documents. To the running of this website, we need your help to support us.

    Thanks to everyone for your continued support.

    No, Thanks