Connecting proliferation and apoptosis in development and disease

Key Points Signals that trigger cell proliferation also trigger programmed cell death. This functions as a protective mechanism against cancer. Control of proliferation-induced cell death is also essential to permit normal tissue growth during development. The Myc proteins have a central role in controlling cell and tissue growth in animals. Myc mutant animals are small. In multicellular tissues, cells compete with one another for growth and survival cues. Myc activity affects the ability of cells to compete. Evidence has begun to accumulate that cell competition has an important role in the control of tissue growth during Drosophila melanogaster development. At present, nothing is known about whether competition has a comparable role in vertebrate development, although this seems likely. Genetic screens for loci affecting tissue growth in D. melanogaster have identified new genes that simultaneously promote proliferation and inhibit apoptosis (or vice versa). Mutations in several of the mammalian orthologues have been linked to specific cancers. Cells grow and divide rapidly during embryonic and postnatal development. Net tissue growth reflects the balance between the addition of new cells and the elimination of existing cells by programmed cell death. Cells compete for growth and survival factors to ensure an appropriate balance between the addition and elimination of cells. Elaborate mechanisms ensure that cells do not evade these constraints, and thereby prevent uncontrolled proliferation.