Lodish • Berk • Kaiser • Krieger • Scott • Bretscher •Ploegh • Matsudaira

MOLECULAR CELL BIOLOGY

SIXTH EDITION

CHAPTER 25
Cancer

©Copyright
2008 W. H.© Freeman
2008 andand
W. H. Freeman Company
Company
 Normal 3T3 Rous sarcoma virus
Transformed 3T3

Every 3 days Transfer at the density of 3x10^5 cell per flask

Spontaneously immortalized, but not transformed yet, cell line
, due to loss of p53 or p19ARF
Multi-hit model
Table 20-2 Molecular Biology of the Cell (© Garland Science 2008)
Table 20-1 Molecular Biology of the Cell (© Garland Science 2008)
 Gain of Function (Oncogene)
Loss of Function (Tumor Suppressor Gene)

Figure 20-27 Molecular Biology of the Cell (© Garland Science 2008)

Figure 20-31 Molecular Biology of the Cell (© Garland Science 2008)
 Gene Alterations

Figure 20-33 Molecular Biology of the Cell (© Garland Science 2008)

DNA AMPLIFICATION in Chr. 4 of Neuroblastoma

Homogenously Staining Region

(HSR) Double Minute Chromosome(DM)
Figure 20-34 Molecular Biology of the Cell (© Garland Science 2008)
Loss of Heterozygosity (LOH)
Red: mutated
---: less established
Oncogenic Mutation
Fusion Mutation
Viral activator
v Src is a constitutively activated form of cSrc

527 Y 인산화는 cSrc를 불활성화

마지막 18aa 이 결실되어있어 늘 활성화

SH2/3: (Rouse Sarcoman virus) Src Homology domain 2/3

BCR-ABL Reciprocal Translocation in CML
Gleevec (Imatinib)은 최초의 표적항암제
Leukemia /Lymphoma에서는 염색체 이상을
전사조절인사 이상이 흔함
Serum PDGF Induces Transcriptional Factors
cMyc Translocation in Burkitt’s Lymphoma
Mutations causing loss of Growth-Inhibiting and Cell Cycle Control
Mutations causing loss of Growth-Inhibiting and Cell Cycle Control

p16 deletion
Cyclin D overexpression
Loss of Tumor suppressor(RB, p53 etc)
RB hyperphosphorylation(inactive)
Viral infection(E7 of HPV)
DNA Damage-induced p53 Pathway in Cancer
Figure 18-6 Molecular Biology of the Cell (© Garland Science 2008)
Figure 18-7 Molecular Biology of the Cell (© Garland Science 2008)
Figure 18-8 Molecular Biology of the Cell (© Garland Science 2008)
Figure 18-9 Molecular Biology of the Cell (© Garland Science 2008)