Gene amplification in human lung cancer. The myc family genes and other proto-oncogenes and growth factor genes.
The development of human lung cancer may require multiple genetic deletions affecting a number of chromosomes, e.g., 1, 3, 11, 13, and 17. These genetic aberrations may induce the activation of proto-oncogenes (c-jun, ras, c-raf1) and the loss of tumor suppressor genes (p53). Some of the activated proto-oncogenes and tumor suppressor genes are more selectively expressed or absent in small-cell lung cancer (L-myc, c-myb, c-scr, Rb gene) or non-small-cell lung cancer (c-erbB-2, c-sis, c-fes). These genes may thus be of importance for selection of differentiation pathway. The c-myc oncogene is frequently amplified in small-cell lung cancer cell lines in a much higher frequency than in vivo. This indicates that c-myc seems to be related to tumor progression and a relatively late event in the lung cancer development. The uncontrolled production of multiple growth factors has been identified in human lung cancer cell lines. These factors can promote and inhibit the proliferation via paracrine and autocrine loops via specific receptors. The products from some of the activated proto-oncogenes (c-sis, c-erbB-2) are sequences homologous to a certain growth factor (PDGF) and a receptor (EGF) identified in lung cancer. The production and action of these growth factors may be of major importance for further activation of proto-oncogenes via intracellular signal transduction and specific oncogenic activation leading to further tumor progression.
Bergh
J C
JC
Department of Oncology, University of Uppsala, Sweden.
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002872:Chromosome Deletion; D005784:Gene Amplification / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D016259:Genes, myc / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011519:Proto-Oncogenes / Q000502:physiology*
D006133:Growth Substances