文档介绍：CARCINOGENESIS:MOLECULAR BASIS OF CANCER
DAVID LEWIN MD
期刊杂志
OVERVIEW
BASIC CONCEPTS OF ONCOGENES, TUMOR SUPPRESSOR GENES, APOPTOSIS, DNA REPAIR & TELOMERES
HOW THEY ARE ASSOCIATED WITH MALIGNANCY
PROPOSED FUNCTIONS
IC ALTERATIONS ASSOCIATED WITH THEIR ACTIVATION OR LOSS
FUNDAMENTAL PRINCIPLES
Non-Lethal ic damage (Mutations)
Acquired Environment (next lecture)
Inherited (Germ line)
Tumors arise from a single progenitor cell
Monoclonal (X-linked isoenzyme)
Target Genes
Proto-oncogenes, TSG, Apoptosis, DNA repair
Multistep Process
MONOCLONALITY:X-Linked Isoenzyme
Polyclonal
Monoclonal
Kumar et al. Basic Pathology 6th ed. Fig. 6-15
Simplified Cancer Pathogenesis
Damage
Gene Expression
Normal
Malignancy
Kumar et al. Basic Pathology 6th ed. Fig. 6-16
ONCOGENES
PROTO-ONCOGENES
NORMAL CELLULAR GENE
ALTERATIONS GIVE ONCOGENE
MUTATIONS, AMPLIFICATION, RETROVIRAL TRANSFER
DEFINE MOLECULAR BASIS FOR CANCER
EXPLAIN MUTAGENS EFFECT ON CANCER DEVELOPMENT
LABORATORY IDENTIFICATION OF ONCOGENES
ACUTE RETROVIRAL TRANSDUCTION
ACUTE TRANSFORMING VIRUSES
(V-ONC)
INSERTIONAL MUTAGENESIS
SLOW TRANSFORMING VIRUSES
DNA TRANSFECTION (IN VITRO)
NOT ASSOCIATED WITH VIRUSES
Protein Products of Oncogenes
Oncoproteins
Resemble normal products except:
Devoid of regulatory elements
Production does not depend on growth factors or external signals
Effect key proteins
Cell growth
Development
Differentiation
Cell Death
PROTO-ONCOGENES
Growth Factors
sis, hst-1, int-2
Over expressed
Growth Factor Receptors
ret, c-erb B-2 (Her2/neu)
Mutated “on”
Signal Transducers
ras: mon abnormality
Mutated “on”
Nuclear Transcription Proteins
myc
Control transcription genes, Bind DNA
Cyclin and Cyclin-Dependent Kinases
Mutations favor proliferation
Model of Action of ras Gene
Kumar et al. Basic Pathology 6th ed. Fig. 6-17