Abstract
Research on growth factors, growth factor receptors and signal transduction pathways have provided an exciting conceptual framework for understanding multistage carcinogenesis1. Fig. 1 displays in schematic form how certain extracellular growth factors are perceived by cellular receptors, which are often located at the cell surface, and how the occupancy of these receptors leads to a cascade of signal transduction, through the cytoplasm and eventually into the nucleus, thus altering patterns of gene expression. This figure also emphasizes the central role that a series of protein kinase enzymes plays in several pathways of signal transduction. A general theme that has emerged is that the proto-oncogenes represent a subset of genes that normally code for components in these pathways of signal transduction. Alterations in the structure and function of these proto-oncogenes can convert them to “activated” oncogenes, which cause aberrations in signal transduction and thus disrupt normal growth, differentiation and inter-cellular coordination.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
I. B. Weinstein, Growth factors, oncogenes and multistage carcinogenesis, J. Cell Biochem. 33:213 (1987).
Y. Nishizuka, Perspectives on the roles of protein kinase C in stimulus-response coupling, J. Natl. Cancer Inst. 76:363 (1986).
M. J. Berridge, Inositol triphosphate and diacylglycerol: Two interacting second messengers, Ann. Rev. of Biochem. 56:159 (1987).
C. A. O’Brian, R. M. Liskamp, D. H. Solomon and I. B. Weinstein, Triphenylethylenes: A new class of protein kinase C inhibitors, J. Natl. Cancer Inst. 76:1243 (1986).
C. House and B. E. Kemp, Protein kinase C contains a pseudosubstrate prototype in its regulatory domain, Science 238:1726 (1987).
G. M. Housey, C. A. O’Brian, M. D. Johnson, P. T. Kirschmeier and I. B. Weinstein, Isolation of cDNA clones encoding protein kinase C: Evidence for a novel protein kinase C-related gene family, Proc. Natl. Acad. Sci. USA 84:1065 (1987).
G. M. Housey, M. D. Johnson, W.-L. Hsiao, C. A. O’Brian, J. P. Murphy, P. Kirschmeier and I. B. Weinstein, Overproduction of protein kinase C causes disordered growth control in rat fibroblasts, Cell 52:343 (1988).
L. Coussens, P. J. Parker, L. Rhee, T. L. Yang-Feng, E. Chen, M. D. Waterfield, U. Francke and A. Ullrich, Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways, Science 233:859 (1986).
J. L. Knopf, M-H. Lee, L. A. Sultzman, R. W. Kriz, C. R. Loomis, R. M. Hewick and R. M. Bell, Cloning and expression of multiple protein kinase C cDNAs, Cell 46:491 (1986).
U. Kikkawa, K. Ogita, Y. Ono, Y. Asaoka, M. S. Shearman, F. Tomoko, K. Ase, K. Sekiguchi, K. Igarashi and Y. Nishizuka, The common structure and activities of four subspecies of rat brain protein kinase C family, FEBS Letters 223:212 (1987).
S. Ohno, H. Kawasaki, S. Imajoh, K. Suzuki, M. Inagaki, H. Yokohura, T. Sakoh and H. Hidaka, Tissue-specific expression of three distinct types of rabbit protein kinase C, Nature 325:161 (1987).
F. L. Huang, Y. Yoshida, H. Nakabayashi, J. L. Knopf, W. S. Young and K.-P. Huang, Immunochemical identification of protein kinase C isozymes as products of discrete genes, Biochem Biophys Res Commun. 149:946 (1987).
P. T. Kirschmeier, G. M. Housey, M. D. Johson, A. S. Perkins and I. B. Weinstein, Construction and characterization of a retroviral vector demonstrating efficient expression of cloned cDNA sequences, DNA in press (1988).
R. Mann, R. C. Mulligan and D. Baltimore, Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus, Cell 33:153 (1983).
M. D. Johnson, G. M. Housey, P. Kirschmeier and I. B. Weinstein, Molecular cloning of gene sequences regulated by tumor promoters and mitogens through protein kinase C, Mol. Cell Biol. 7:2821 (1987).
C. J. Fitzer, C. A. O’Brian, J. G. Guillem and I. B. Weinstein, The regulation of protein kinase C by chenodeoxycholate, deoxycholate and several related bile acids, Carcinogenesis 8:217 (1987).
J. G. Guillem, C. A. O’Brian, C. J. Fitzer, M. D. Johnson, K. A. Forde, P. LoGerfo and I. B. Weinstein, Studies on protein kinase C and colon carcinogenesis, Arch. Sur. 122:1475 (1987).
L. L. Hsieh, W.-L. Hsiao, C. Peraino, R. R. Maronpot and I. B. Weinstein, Expression of retroviral sequences and oncogenes in rat liver tumors induced by diethylnitrosamine, Cancer Research 47:3421 (1987).
L. L. Hsieh, C. Peraino and I. B. Weinstein, Expression of endogenous retrovirus-like sequences and cellular oncogenes during phenobarbital treatment and regeneration in rat liver, Cancer Research 48:265 (1988).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Springer Science+Business Media New York
About this chapter
Cite this chapter
Weinstein, I.B. et al. (1988). New Insights into Tumor Promotion from Molecular Studies of Protein Kinase C. In: Feo, F., Pani, P., Columbano, A., Garcea, R. (eds) Chemical Carcinogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9640-7_21
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9640-7_21
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9642-1
Online ISBN: 978-1-4757-9640-7
eBook Packages: Springer Book Archive