Sp10 BIO314 Ch7BB

Sp10 BIO314 Ch7BB - RobertA.Weinberg TheBiologyofCancer...

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The Biology of Cancer First Edition Chapter 7: Tumor Suppressor Genes Copyright © Garland Science 2007 Robert A. Weinberg
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Tumor Suppressor Genes In a complex and tightly controlled system,  growth  promoting signals are likely to be  counterbalanced by growth-inhibitory signals. The genes encoding these anti-growth proteins are  called tumor suppressor genes. The loss of these genes contributes to cancer.
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Figure 20-14 Molecular Biology of the Cell (© Garland Science 2008)
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Figure 7.1 The Biology of Cancer (© Garland Science 2007) The concept of a tumor suppressor developed from experiments which demonstrated that, in  some instances, the cancer  phenotype is  recessive  to normal growth. This was inconsistent with activated oncogene-driven transformation (ie tumor  virus), which is clearly dominant over normal  signaling. Cell fusion
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Figure 7.3 The Biology of Cancer (© Garland Science 2007) Often, the hybrid cell had  lost the ability to induce tumors in mice. If the cancer cell  was transformed by a tumor virus, often the cancer phenotype was  dominant. If not, the cancer pheno- type was usually recessive. 
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One explanation for the recessive cancer  phenotype is that these cancer cells have lost  a growth-inhibitory gene, and fusion with a  normal cell provides this gene, along with  growth inhibition. The concept of “tumor suppressors”, negative  regulators of cell growth,  that are lost in  cancer cells. This hypothesis was favored because loss-of-
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Figure 20-27 Molecular Biology of the Cell (© Garland Science 2008)
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Figure 7.4a The Biology of Cancer (© Garland Science 2007) Retinoblastoma (Rb) is the first tumor suppressor gene These pediatric tumors arise  from retinal stem cell precursors Sporadic (no family history) (1/20,000 children) Familial (family history) The familial form is characterized by  bilateral, multifocal eye tumors, and  increased risk of other tumors later in  life
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Figure 7.5a The Biology of Cancer (© Garland Science 2007) familial sporadic
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Figure 7.6 The Biology of Cancer (© Garland Science 2007) The Knudson hypothesis: proposes that familial, due to the inherited allele, re- quires only one additional “genetic hit” (somatic mutation) for disease. Sporadic requires 2 indep- endent “hits”, explains  delay and decreased  incidence familial sporadic Knudson: kinetics of rate of appearance of tumors
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A geneticist and physician, Dr. Knudson is internationally recognized for his "two- hit" theory of cancer causation, which explained the relationship between the  hereditary and non-hereditary forms of a cancer and predicted the existence of  tumor-suppressor genes that can suppress cancer cell growth. This now- confirmed theory has advanced understanding of errors in the genetic program  that turn normal cells into cancer cells. http://www.fccc.edu/news/knudson/bio.html
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Figure 20-30 Molecular Biology of the Cell (© Garland Science 2008)
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Figure 7.7
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This note was uploaded on 01/04/2011 for the course BIO 314 taught by Professor Erster,s during the Spring '08 term at SUNY Stony Brook.

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Sp10 BIO314 Ch7BB - RobertA.Weinberg TheBiologyofCancer...

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