Chapter 17: Regulation of cell number [omit material on cell cycle regulation, apoptosis, cell signalling (pp. 548-558) – covered in BIO 315] Cell number is regulated by two primary systems: Cell cycle control Apoptosis control Fig. 17-1

Cancer: malignant tumor; clone of cells that have lost normal cell growth regulation - result from sequential mutations in genes that regulate cell growth Oncogene: dominant, gain-of-function mutation causes cancer - originally identified in tumor viruses which transduce the gene into cells (e.g., v-ras) - correspond to normal genes that regulate cell growth in cells (e.g., c-ras)

Ras oncogene is a mutant form of the normal Ras gene Fig. 17-12 (regulated cell proliferation)

Ras oncogene is a mutant form of the normal Ras gene mutation Fig. 17-12 Fig. 17-16 (regulated cell proliferation) (constitutive cell proliferation→tumor)

Ras oncogene is a mutant form of the normal Ras gene mutation Fig. 17-12 Fig. 17-16 (regulated cell proliferation) (constitutive cell proliferation→tumor)

The v-erB oncogene is a truncated EGF receptor gene Fig. 17-17

The v-erB oncogene is a truncated EGF receptor gene Fig. 17-17

Chronic myelogenous leukemia is caused by reciprocal translocation known as the “Philadelphia chromosome (regulated protein tyrosine kinase) Fig. 17-18

Chronic myelogenous leukemia is caused by reciprocal translocation known as the “Philadelphia chromosome (unregulated protein tyrosine kinase → unregulated cell proliferation) Why is this translocation not inherited? Why is proliferation limited to leukocytes? Fig. 17-18

Tumor-suppressor genes: wild-type alleles negatively regulate cell growth or positively regulate cell death - cancer-causing alleles are usually recessive, loss-of-function mutations - cell must be homozygous for the mutation to exhibit a tumor phenotype - alleles can be inherited; homozygosity arises by somatic mutation or mitotic crossingover

The Rb protein is an E2F tethering protein required for cell cycle regulation Loss of Rb results in constitutive E2F activation → unregulated cell proliferation Fig. 17-4

Fig. 17-20

Fig. 17-20

Recommended problems in Chapter 17: 8, 9, 11, 12, 22

Fig. 17-