504 art Iv The Immune System in Health and disease TABLE 22-1 Functional classification of cancer-associated genes lype/name Nature af gene product ATEGORY L: GENES THAT INDUCE CELLULAR PROLIFERATION Growth factors A form of platelet-derived growth factor(PDGF) Growth-factor receptors Receptor for colony-stimulating factor 1(CSF-1) Receptor for epidermal growth factor(EGF) Protein(HER2)related to EGF receptor Receptor for thyroid hormone lyrosine kinase Ha-ras GTP-binding protein with GTPase activity N-ras GTP-binding protein with GTPase activity K-ras GTP-binding protein with GTPase activity Transcription factors Component of transcription factor AP fos Component of transcription factor AP ayc DNA-binding protein CATEGORY II: TUMOR SUPRESSOR GENES. INHIBITORS OF CELLULAR PROLIFERATION Rb Suppressor of retinoblastoma Nuclear phosphoprotein that inhibits formation of small-cell lung cander and colon cancers DCC pressor of colon carcinoma pressor of adenomatous polyposis NFl Suppressor of neurofibromatosis WIT Suppressor of Wilms tumor CATEGORY III: GENES THAT REGULATE PROGRAMMED CELL DEATH The activity of the normal products of the category ll genes inhibits progression of the cell cycle. Loss of a gene or its inactivation by mutation in an indicated tumor-suppressor gene is associated with development of the indicated cancers. 50% of breast and colon cancers have been shown to be Proto-Oncogenes Can Be Converted ed with mutations in p5. to Oncogenes REGULATION OF PROGRAMMED CELL DEATH In 1972, R J. Huebner and G I Todaro suggested that muta A third category of cancer-associated genes regulates pro- tions or genetic rearrangements of proto-oncogenes by car- grammed cell death. These genes encode proteins that either cinogens or viruses might alter the normally regulated function block or induce apoptosis. Included in this category of onco- of these genes, converting them into potent cancer-causing genes is bcl-2, an anti-apoptosis gene. This oncogene was oncogenes( Figure 22-2). Considerable evidence supporting originally discovered because of its association with B-cell fol- this hypothesis accumulated in subsequent years. For example licular lymphoma. Since its discovery, bd-2 has been shown to some malignantly transformed cells contain multiple copies of lay an important role in regulating cell survival cellular oncogenes, resulting in increased production of onco hematopoiesis and in the survival of selected B cells and gene products. Such amplification of cellular oncogenes has T cells during maturation. Interestingly, the Epstein-Barr been observed in cells from various types of human cancers. virus contains a gene that has sequence homology to bd-2 Several groups have identified c-myc oncogenes in homo- and may act in a similar manner to suppress apoptosis. geneously staining regions(HSRs)of chromosomes from canover 50% of breast and colon cancers have been shown to be associated with mutations in p53. REGULATION OF PROGRAMMED CELL DEATH A third category of cancer-associated genes regulates pro￾grammed cell death. These genes encode proteins that either block or induce apoptosis. Included in this category of onco￾genes is bcl-2, an anti-apoptosis gene. This oncogene was originally discovered because of its association with B-cell fol￾licular lymphoma. Since its discovery, bcl-2 has been shown to play an important role in regulating cell survival during hematopoiesis and in the survival of selected B cells and T cells during maturation. Interestingly, the Epstein-Barr virus contains a gene that has sequence homology to bcl-2 and may act in a similar manner to suppress apoptosis. Proto-Oncogenes Can Be Converted to Oncogenes In 1972, R. J. Huebner and G. J. Todaro suggested that muta￾tions or genetic rearrangements of proto-oncogenes by car￾cinogens or viruses might alter the normally regulated function of these genes, converting them into potent cancer-causing oncogenes (Figure 22-2). Considerable evidence supporting this hypothesis accumulated in subsequent years. For example, some malignantly transformed cells contain multiple copies of cellular oncogenes, resulting in increased production of onco￾gene products. Such amplification of cellular oncogenes has been observed in cells from various types of human cancers. Several groups have identified c-myc oncogenes in homo￾geneously staining regions (HSRs) of chromosomes from can- 504 PART IV The Immune System in Health and Disease TABLE 22-1 Functional classification of cancer-associated genes Type/name Nature of gene product CATEGORY I: GENES THAT INDUCE CELLULAR PROLIFERATION Growth factors sis A form of platelet-derived growth factor (PDGF) Growth-factor receptors fms Receptor for colony-stimulating factor 1 (CSF-1) erbB Receptor for epidermal growth factor (EGF) neu Protein (HER2) related to EGF receptor erbA Receptor for thyroid hormone Signal transducers src Tyrosine kinase abl Tyrosine kinase Ha-ras GTP-binding protein with GTPase activity N-ras GTP-binding protein with GTPase activity K-ras GTP-binding protein with GTPase activity Transcription factors jun Component of transcription factor AP1 fos Component of transcription factor AP1 myc DNA-binding protein CATEGORY II: TUMOR-SUPRESSOR GENES, INHIBITORS OF CELLULAR PROLIFERATION* Rb Suppressor of retinoblastoma p53 Nuclear phosphoprotein that inhibits formation of small-cell lung cander and colon cancers DCC Suppressor of colon carcinoma APC Suppressor of adenomatous polyposis NF1 Suppressor of neurofibromatosis WT1 Suppressor of Wilm’s tumor CATEGORY III: GENES THAT REGULATE PROGRAMMED CELL DEATH bcl-2 Suppressor of apoptosis * The activity of the normal products of the category II genes inhibits progression of the cell cycle. Loss of a gene or its inactivation by mutation in an indicated tumor-suppressor gene is associated with development of the indicated cancers