清华大学：《分子生物学》（英文版）Chapter 28 Oncogenes and cancer

Chapter 28 Oncogenes and cancer 莘大

Chapter 28 Oncogenes and cancer

28.1 Introduction 28.2 Transforming viruses carry oncogenes 28.3 Early genes of dna transforming viruses have multifunction oncogenes 28.4 Retroviruses activate or incorporate cellular genes 28.5 Retroviral oncogenes have cellular counterparts 28.6 Ras oncogenes can be detected in a transfection assay 28.7 Ras proto-oncogenes can be activated by mutation at specific positions 28.8 Nondefective retroviruses activate proto-oncogenes 28.9 Proto-oncogenes can be activated by translocation 28. 10 The Philadelphia translocation generates a new oncogene 28 11 Oncogenes code for components of signal transduction cascades 28. 12 Growth factor receptor kinases can be mutated to oncogenes 28 13 Src is the prototype for the proto-oncogenic cytoplasmic tyrosine kinases 28 14 Oncoproteins may regulate gene expression 28 15 RB is a tumor suppressor that controls the cell cycle 28. 16 Tumor suppressor p53 suppresses growth or triggers apoptosis 28 17 p53 is a dna-binding protein 28.18 p53 is controlled by other tumor suppressors and oncogenes 28.19 Immortalization and transformation are independent 28 20 Telomere shortening causes cell mortalit 请莘大

28.1 Introduction 28.2 Transforming viruses carry oncogenes 28.3 Early genes of DNA transforming viruses have multifunction oncogenes 28.4 Retroviruses activate or incorporate cellular genes 28.5 Retroviral oncogenes have cellular counterparts 28.6 Ras oncogenes can be detected in a transfection assay 28.7 Ras proto-oncogenes can be activated by mutation at specific positions 28.8 Nondefective retroviruses activate proto-oncogenes 28.9 Proto-oncogenes can be activated by translocation 28.10 The Philadelphia translocation generates a new oncogene 28.11 Oncogenes code for components of signal transduction cascades 28.12 Growth factor receptor kinases can be mutated to oncogenes 28.13 Src is the prototype for the proto-oncogenic cytoplasmic tyrosine kinases 28.14 Oncoproteins may regulate gene expression 28.15 RB is a tumor suppressor that controls the cell cycle 28.16 Tumor suppressor p53 suppresses growth or triggers apoptosis 28.17 p53 is a DNA-binding protein 28.18 p53 is controlled by other tumor suppressors and oncogenes 28.19 Immortalization and transformation are independent 28.20 Telomere shortening causes cell mortality

28. Introduction Anchorage dependence describes the need of normal eukaryotic cells for a surface to attach to in order to grow in culture Aneuploid chromosome constitution differs from the usual diploid constitution by loss or duplication of chromosomes or chromosomal segments Metastasis describes the ability of tumor cells to leave their site of origin and migrate to other locations in the body, where a new colony is established Monolayer describes the growth of eukaryotic cells in culture as a layer only one cell deep Oncogenes are genes whose products have the ability to transform eukaryotic cells so that they grow in a manner analogous to tumor cells. Oncogenes carried by retroviruses have names of the form v-onc 消当

Anchorage dependence describes the need of normal eukaryotic cells for a surface to attach to in order to grow in culture. Aneuploid chromosome constitution differs from the usual diploid constitution by loss or duplication of chromosomes or chromosomal segments. Metastasis describes the ability of tumor cells to leave their site of origin and migrate to other locations in the body, where a new colony is established. Monolayer describes the growth of eukaryotic cells in culture as a layer only one cell deep. Oncogenes are genes whose products have the ability to transform eukaryotic cells so that they grow in a manner analogous to tumor cells. Oncogenes carried by retroviruses have names of the form v-onc. 28.1 Introduction

28.1Introduction Primary cells are eukaryotic cells taken into culture directly from the animal Proto-oncogenes are the normal counterparts in the eukaryotic genome to the oncogenes carried by some retroviruses. They are given names of the form c-onc Serum dependence describes the need of eukaryotic cells for factors contained in serum in order to grow in culture Transformation of bacteria describes the acquisition of new genetic markers by incorporation of added dna 消当

Primary cells are eukaryotic cells taken into culture directly from the animal. Proto-oncogenes are the normal counterparts in the eukaryotic genome to the oncogenes carried by some retroviruses. They are given names of the form c-onc . Serum dependence describes the need of eukaryotic cells for factors contained in serum in order to grow in culture. Transformation of bacteria describes the acquisition of new genetic markers by incorporation of added DNA. 28.1 Introduction

uitre ages tor severa dysons③ Growth of cells is restricted by propertes 8 of individual tissue 28.1 Introduction jority of cells die: a few cells⑨g grow o Immortalizatio Established cell line divides but cells continue m adhere to substratum equire serum, and are bited by contact o Figure 28. 1 Three types of properties distinguish a cancer Transfom ation Transformed cells are independe of anchorage, serum, contact cell from a normal cell inhi bition: change shape, round up. and grow into a focus Sequential changes in cultured cells can be correlated with Transformed cells may form solid tumor changes in tumorigenicity NOw fully tumorigenic, cells become mobile and can migrate to start new colonies 消当 Tumors form at new locations

Figure 28.1 Three types of properties distinguish a cancer cell from a normal cell. Sequential changes in cultured cells can be correlated with changes in tumorigenicity. 28.1 Introduction

uitre ages tor severa dysons③ Growth of cells is restricted by propertes 8 of individual tissue 28.1 Introduction jority of cells die: a few cells⑨g grow o Immortalizatio Established cell line divides but cells continue m adhere to substratum equire serum, and are bited by contact o Figure 28. 1 Three types of properties distinguish a cancer Transfom ation Transformed cells are independe of anchorage, serum, contact cell from a normal cell inhi bition: change shape, round up. and grow into a focus Sequential changes in cultured cells can be correlated with Transformed cells may form solid tumor changes in tumorigenicity NOw fully tumorigenic, cells become mobile and can migrate to start new colonies 消当 Tumors form at new locations

Figure 28.1 Three types of properties distinguish a cancer cell from a normal cell. Sequential changes in cultured cells can be correlated with changes in tumorigenicity. 28.1 Introduction

28.1Introduction Normal cells Transformed cells 遇 Figure 28.2 Normal fibroblasts grow as a layer of flat, spread-out cells, whereas transformed fibroblasts are rounded up and grow in cell masses. The cultures on the left contain normal cells, those on the right contain transformed cells. The top views are by conventional microscopy, the bottom by scanning electron microscopy Photographs kindly provided by Hidesaburo Hanafusa and J. Michael Bishop 消当

Figure 28.2 Normal fibroblasts grow as a layer of flat, spread-out cells, whereas transformed fibroblasts are rounded up and grow in cell masses. The cultures on the left contain normal cells, those on the right contain transformed cells. The top views are by conventional microscopy, the bottom by scanning electron microscopy. Photographs kindly provided by Hidesaburo Hanafusa and J. Michael Bishop. 28.1 Introduction

28.2 Transforming viruses carry oncogenes Mral Class Genome Genome Size Oncogenes Origin of Oncogene Action of Oncogene Pol yoma csDNA 5-6kb T antigens Early viral gene inactivates tumar suppressor HPY dDN鸟 8 kb E6&E7 Early viral gene inactivates tumar suppressor Adeno csDN 37kb E1A&ElB Early viral gene activates tumor suppressor Retrovirus ssRNA 6-9 kb Indi vidual Cellular activates oncogenic pathway acute) Figure 28.3 Transforming viruses may carry oncogenes 消当

Figure 28.3 Transforming viruses may carry oncogenes. 28.2 Transforming viruses carry oncogenes

Productiv e infection Transformation 28.2 Transforming (in permissi e cells)(nonpermissive cells) viruses carr Early infe ction Abortiv e infe ction oncogenes Entry and VIrus enters production of virus components Figure 28.4 Permissive cells o Late infection Inte gration Replication Viral DNA are productively infected by S and assembly becomes part of particles of host genom a dna tumor virus that enters the lytic cycle, while nonpermissive cells are LySis Transformation Cell de ath Cells change transformed to change their and release shape and of viruses 「W phenotype 消当

Figure 28.4 Permissive cells are productively infected by a DNA tumor virus that enters the lytic cycle, while nonpermissive cells are transformed to change their phenotype. 28.2 Transforming viruses carry oncogenes

28.2 Transforming ear late viruses carr s40 oncogenes Infection Adenovirus ear late Figure 28.5 Cells AMA transformed by polyomaviruses or Host dNa adenoviruses have viral Integrated sequences that include the 八 AAVA early region integrated into the cellular genome. Sites of Transforming integration are random onco otein Sv40 T/t antigens Adenovirus E1A, E1B 消当

Figure 28.5 Cells transformed by polyomaviruses or adenoviruses have viral sequences that include the early region integrated into the cellular genome. Sites of integration are random. 28.2 Transforming viruses carry oncogenes