Differential expression of myc family genes during murine development

Kathryn A. Zimmerman, George D. Yancopoulos, Robert G. Collum, Russell K. Smith, Nancy E. Kohl, Kathleen A. Denis, Marion M. Nau, Owen N. Witte, Dominique Toran-Allerand, Connie E. Gee, John D. Minna, Frederick W. Alt

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327 Scopus citations

Abstract

The myc family of cellular oncogenes contains three known members. The N-myc and c-myc genes have 5′-noncoding exons, strikingly homologous coding regions1-3, and display similar oncogenic potential in an in vitro transformation assay4,5. The L-myc gene is less well characterized, but shows homology to N-myc and c-myc (ref. 6; also see below), c-myc is expressed in most dividing cells, and deregulated expression of this gene has been implicated in the development of many classes of tumours 7. In contrast, expression of N-myc has been found only in a restricted set of tumours, most of which show neural characteristics; these include human neuroblastoma8-10, retinoblastoma10,11 and small cell lung carcinoma (SCLC)12. L-myc expression has so far been found only in SCLC6. Activated N-myc and L-myc expression has been implicated in oncogenesis4-6,11,12; for example, although N-myc expression has been found in all neuroblastomas tested9,10, activated (greatly increased) N-myc expression, resulting from gene amplification 8,13,14, is correlated with progression of the tumour15. We now report that high-level expression of N- and L-myc is very restricted with respect to tissue and stage in the developing mouse, while that of c-myc is more generalized. Furthermore, we demonstrate that N-myc is not simply a neuroectoderm-specific gene; both N- and L-myc seem to be involved in the early stages of multiple differentiation pathways. Our findings suggest that differential myc gene expression has a role in mammalian development and that the normal expression patterns of these genes generally predict the types of tumours in which they are expressed or activated.

Original languageEnglish (US)
Pages (from-to)780-783
Number of pages4
JournalNature
Volume319
Issue number6056
DOIs
StatePublished - Dec 1 1986

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    Zimmerman, K. A., Yancopoulos, G. D., Collum, R. G., Smith, R. K., Kohl, N. E., Denis, K. A., Nau, M. M., Witte, O. N., Toran-Allerand, D., Gee, C. E., Minna, J. D., & Alt, F. W. (1986). Differential expression of myc family genes during murine development. Nature, 319(6056), 780-783. https://doi.org/10.1038/319780a0