Experimental Cell Research 173 (1987) 1-16 SPECIAL ARTICLE Cancer Genes, Proto-oncogenes, and Development ROLF I. OHLSSON*” and SUSAN B. PFEIFER-OHLSSON*’ t *Centre for Biotechnology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden, and t Department of Pediatrics, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden The retroviral cancer genes have in a number of observations been shown to interfere with the developmental program of target cells. Here we are concerned with the interface between cancer genes/proto-oncogenes and developmental processes. Research in this field serves two purposes; to delineate key developmental controls and to identify these as kt@etS for OnCOgenk agentS. 0 1987 Academic Press, Inc. The complex pattern of development of a single egg into an adult animal involves space-time control of cell populations of various numbers and lineages. Thus, invasive and proliferative cells of early embryogenic cell lineages are replaced by more mature cell phenotypes, which eventually become organized into tissues, where the controlled expression of specialized features determines the shape and function of each individual organ. In the adult animal, analogous developmental situations are represented by the lineage-specific production of hematopoietic cells from immature bone marrow stem cells. Perturbation of developmental controls, indirectly or directly involved in cell maturation, may lead to congenital anomalies and embryonic death, and also to unrestrained cell growth of cancer. Indeed, this fine line between “normal” and tumor-like behavior of embryonic cells has for decades nurtured the idea that key developmental controls of the normal cell phenotype malfunction during the process of neoplastic transformation and tumor progression [l-3]. Thus, many of the important features of the tumor phenotype, such as rapid growth, tissue invasiveness, cell immortalization, and evasiveness of immunosuppression, may represent analogs or homologs of normal events. During development in general and embryogenesis in particular, such features are likely to be transiently coex- pressed in complex patterns to maintain proper growth and development. The advent of molecular biology techniques coupled with studies on RNA tumor viruses (retroviruses) has opened up new possibilities to define such important regulatory processes at the molecular level in normal and neoplastic phenotypes. ’ To whom reprint requests should be addressed. Copyright @ 1987 by Academic F’ress. Inc. Au rights of reproduction in any form reserved 0014-4827187 $03.00