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Neoplasia 4a

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									Molecular basis of cancer

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Oncogene (GFR). Tyrosine kinase receptor (neurotropic factors) Dimerization & activation; substrate specificity altered. MEN types 2A (thy, adr, parathy), 2B (thy, adr )and familial medullary thyroid carcinoma. Complete loss: Hirschsprung disease.

RAS Oncogene
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Single most common abnormality of dominant oncogenes in human tumors. 90% pancreatic adenoca. K, cholangioca. 50% colon K, endometrial, thyroid. 30% lung adenoca., myeloid leukemias N.

Growth factors-EGF, PDGF, CSF-1

Growth factor receptor

Activation of RAS

GF Cell membrane GFR

Inactive RAS Active RAS P

Activation of MAP kinase pathway
Nucleus Activation of transcription

RAS contd..
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Signal transducing protein. GTPase-activating proteins (GAPs): brake. Mutations of RAS: brake falters. Neurofibromin NF-1: GAP. BRAF: 80% benign nevi.

MYC Oncogene
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Induced when quiescent cell receives a signal to divide. Histone acety. MYC protein Nucleus ↓ cell adhesion MAX protein Target genes ↑ cell motility ↑ protein synthesis Trascriptional activator: ↓ proteinase activity Ornithine decarboxylase, cyclin D2

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MYC contd..
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C-MYC : Burkitt lymphoma N-MYC : Neuroblastoma, small cell carcinoma of lung L-MYC : Small cell carcinoma of lung Breast, colon, lung and other Cas.


								
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