This UCLA Symposium will address the rapidly expanding array of mechanisms that negatively regulate cell growth. These mechanisms and their corollaries include: (1) Homozygosities acquired at specific chromosomal loci during tumor progression which are thought to reflect the inactivation of negative regulators of cell growth, resulting in the unleashing of stem cell growth. These genes are termed """"""""anti-oncogenes and tumor suppressor genes"""""""". (2) Loci conferring high risk, heritable transmission of tumor susceptibility (e.g., familial retinoblastoma and polyposis coli) which may soon be revealed as similar to or distinct from """"""""anti-oncogenes"""""""". (3) Growth-suppressing genes in normal cells which suppress tumor cell malignancy upon somatic cell hybridization. These genes may be partially overlapping with those discovered through karyotypic and RFLP analyses. (4) Distinct genes created by transformation with oncogenes. Such genes have been associated with reversion from a tumorigenic phenotype and they have been shown to antagonize the action of oncogenes. (5) Cellular mechanisms which inhibit the growth of other cells in close proximity, limiting tumorigenesis and maintaining normal tissue architecture; in some cases through establishing direct connections between apposed cells. (6) TGF-b, b-interferon, and TNF are known growth inhibitory factors. TGF-b in turn subsumes an increasingly large group of related polypeptide regulators of differentiation in developing vertebrates and invertebrates (e.g., Mullerian inhibiting factor). And, finally (7) Developmental growth inhibiting mechanisms induced with terminal (or end-stage) differentiation. Session Topic Include: Genetics of Human Cancer (Somatic Alteration, Familial Tumors); Growth-Suppressing Genes; Somatic Cell Genetics; Oncogene-Reverting Genes; Intercellular Mediators of Negative Growth Control; Negatively Acting Diffusable Factors.
