Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1991 Jun;93:51–56. doi: 10.1289/ehp.919351

Differential gene expression during multistage carcinogenesis.

G T Bowden 1, P Krieg 1
PMCID: PMC1568073  PMID: 1773801

Abstract

The use of the mouse skin multistage model of carcinogenesis has aided our understanding of critical target genes in chemical carcinogenesis. The mutagenic activation of the Harvey-ras proto-oncogene has been found to be an early event associated with the initiation of mouse skin tumors by the polycyclic aromatic hydrocarbon 7,12 dimethylbenz[alpha]anthracene and the pure initiator ethyl carbamate (urethane). In contrast to chemical initiation of mouse skin tumors, ionizing radiation-initiated malignant skin tumors have been shown to possess distinct non-ras transforming gene(s). Differential screening of cDNA libraries made from chemically initiated malignant skin tumors has been used to identify a number of cellular gene transcripts that are overexpressed during mouse skin tumor progression. These differentially expressed genes include beta-actin, ubiquitin, a hyperproliferative keratin (K6), a gene whose product is a member of a fatty acid or lipid-binding protein family, and a gene called transin or stromelysin. The overexpression of the stromelysin gene, which encodes a metalloproteinase that degrades proteins in the basement membrane, is hypothesized to play a functional role in malignant tumor cell invasion and metastasis. We believe that the cloning, identification, and characterization of gene sequences that are differentially expressed during tumor progression could lead to the discovery of gene products that either play functional roles in skin tumor progression or in the maintenance of various progressive tumor phenotypes.

Full text

PDF
51

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antecol M. H., Darveau A., Sonenberg N., Mukherjee B. B. Altered biochemical properties of actin in normal skin fibroblasts from individuals predisposed to dominantly inherited cancers. Cancer Res. 1986 Apr;46(4 Pt 1):1867–1873. [PubMed] [Google Scholar]
  2. Balmain A., Pragnell I. B. Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature. 1983 May 5;303(5912):72–74. doi: 10.1038/303072a0. [DOI] [PubMed] [Google Scholar]
  3. Balmain A., Ramsden M., Bowden G. T., Smith J. Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature. 1984 Feb 16;307(5952):658–660. doi: 10.1038/307658a0. [DOI] [PubMed] [Google Scholar]
  4. Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
  5. Bizub D., Wood A. W., Skalka A. M. Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6048–6052. doi: 10.1073/pnas.83.16.6048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bonham K., Embry T., Gibson D., Jaffe D. R., Roberts R. A., Cress A. E., Bowden G. T. Activation of the cellular Harvey ras gene in mouse skin tumors initiated with urethane. Mol Carcinog. 1989;2(1):34–39. doi: 10.1002/mc.2940020106. [DOI] [PubMed] [Google Scholar]
  7. Borek C., Ong A., Mason H. Distinctive transforming genes in x-ray-transformed mammalian cells. Proc Natl Acad Sci U S A. 1987 Feb;84(3):794–798. doi: 10.1073/pnas.84.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bowden G. T. Chemical carcinogenesis and the oncogenes--a Chemical Pathology Study Section Workshop. Cancer Res. 1985 Feb;45(2):914–918. [PubMed] [Google Scholar]
  9. Chin J. R., Murphy G., Werb Z. Stromelysin, a connective tissue-degrading metalloendopeptidase secreted by stimulated rabbit synovial fibroblasts in parallel with collagenase. Biosynthesis, isolation, characterization, and substrates. J Biol Chem. 1985 Oct 5;260(22):12367–12376. [PubMed] [Google Scholar]
  10. Dahl G. A., Miller J. A., Miller E. C. Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate. Cancer Res. 1978 Nov;38(11 Pt 1):3793–3804. [PubMed] [Google Scholar]
  11. Demmer L. A., Birkenmeier E. H., Sweetser D. A., Levin M. S., Zollman S., Sparkes R. S., Mohandas T., Lusis A. J., Gordon J. I. The cellular retinol binding protein II gene. Sequence analysis of the rat gene, chromosomal localization in mice and humans, and documentation of its close linkage to the cellular retinol binding protein gene. J Biol Chem. 1987 Feb 25;262(6):2458–2467. [PubMed] [Google Scholar]
  12. Finch J. S., Bonham K., Krieg P., Bowden G. T. Murine polyubiquitin mRNA sequence. Nucleic Acids Res. 1990 Apr 11;18(7):1907–1907. doi: 10.1093/nar/18.7.1907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gates R. E., Rees R. S. Altered vitamin A-binding proteins in carcinoma of the head and neck. Cancer. 1985 Dec 1;56(11):2598–2604. doi: 10.1002/1097-0142(19851201)56:11<2598::aid-cncr2820561111>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  14. Hennings H., Shores R., Wenk M. L., Spangler E. F., Tarone R., Yuspa S. H. Malignant conversion of mouse skin tumours is increased by tumour initiators and unaffected by tumour promoters. Nature. 1983 Jul 7;304(5921):67–69. doi: 10.1038/304067a0. [DOI] [PubMed] [Google Scholar]
  15. Jaffe D. R., Bowden G. T. Detection of distinct transforming genes in X-ray induced tumors. Carcinogenesis. 1989 Dec;10(12):2243–2247. doi: 10.1093/carcin/10.12.2243. [DOI] [PubMed] [Google Scholar]
  16. Jaffe D. R., Bowden G. T. Ionizing radiation as an initiator in the mouse two-stage model of skin tumor formation. Radiat Res. 1986 May;106(2):156–165. [PubMed] [Google Scholar]
  17. Jaffe D. R., Williamson J. F., Bowden G. T. Ionizing radiation enhances malignant progression of mouse skin tumors. Carcinogenesis. 1987 Nov;8(11):1753–1755. doi: 10.1093/carcin/8.11.1753. [DOI] [PubMed] [Google Scholar]
  18. Jaffe D., Bowden G. T. Ionizing radiation as an initiator: effects of proliferation and promotion time on tumor incidence in mice. Cancer Res. 1987 Dec 15;47(24 Pt 1):6692–6696. [PubMed] [Google Scholar]
  19. Klein G. The approaching era of the tumor suppressor genes. Science. 1987 Dec 11;238(4833):1539–1545. doi: 10.1126/science.3317834. [DOI] [PubMed] [Google Scholar]
  20. Krieg P., Finch J., Füstenberger G., Melber K., Matrisian L. M., Bowden G. T. Tumor promoters induce a transient expression of tumor-associated genes in both basal and differentiated cells of the mouse epidermis. Carcinogenesis. 1988 Jan;9(1):95–100. doi: 10.1093/carcin/9.1.95. [DOI] [PubMed] [Google Scholar]
  21. Krolewski B., Little J. B. Molecular analysis of DNA isolated from the different stages of x-ray-induced transformation in vitro. Mol Carcinog. 1989;2(1):27–33. doi: 10.1002/mc.2940020105. [DOI] [PubMed] [Google Scholar]
  22. Matrisian L. M., Bowden G. T., Krieg P., Fürstenberger G., Briand J. P., Leroy P., Breathnach R. The mRNA coding for the secreted protease transin is expressed more abundantly in malignant than in benign tumors. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9413–9417. doi: 10.1073/pnas.83.24.9413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Matrisian L. M., Glaichenhaus N., Gesnel M. C., Breathnach R. Epidermal growth factor and oncogenes induce transcription of the same cellular mRNA in rat fibroblasts. EMBO J. 1985 Jun;4(6):1435–1440. doi: 10.1002/j.1460-2075.1985.tb03799.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Melber K., Krieg P., Fürstenberger G., Marks F. Molecular cloning of sequences activated during multi-stage carcinogenesis in mouse skin. Carcinogenesis. 1986 Feb;7(2):317–322. doi: 10.1093/carcin/7.2.317. [DOI] [PubMed] [Google Scholar]
  25. Miller J. A., Miller E. C. The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole. Br J Cancer. 1983 Jul;48(1):1–15. doi: 10.1038/bjc.1983.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mirvish S. S. The carcinogenic action and metabolism of urethan and N-hydroxyurethan. Adv Cancer Res. 1968;11:1–42. doi: 10.1016/s0065-230x(08)60386-3. [DOI] [PubMed] [Google Scholar]
  27. Ostrowski L. E., Finch J., Krieg P., Matrisian L., Patskan G., O'Connell J. F., Phillips J., Slaga T. J., Breathnach R., Bowden G. T. Expression pattern of a gene for a secreted metalloproteinase during late stages of tumor progression. Mol Carcinog. 1988;1(1):13–19. doi: 10.1002/mc.2940010106. [DOI] [PubMed] [Google Scholar]
  28. Ostrowski L. E., Krieg P., Finch J., Cress A. E., Nagle R. B., Bowden G. T. Expression of beta-actin during progression of mouse skin tumors. Carcinogenesis. 1989 Aug;10(8):1439–1444. doi: 10.1093/carcin/10.8.1439. [DOI] [PubMed] [Google Scholar]
  29. Pelling J. C., Ernst S. M., Strawhecker J. M., Johnson J. A., Nairn R. S., Slaga T. J. Elevated expression of Ha-ras is an early event in two-stage skin carcinogenesis in SENCAR mice. Carcinogenesis. 1986 Sep;7(9):1599–1602. doi: 10.1093/carcin/7.9.1599. [DOI] [PubMed] [Google Scholar]
  30. Quintanilla M., Brown K., Ramsden M., Balmain A. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature. 1986 Jul 3;322(6074):78–80. doi: 10.1038/322078a0. [DOI] [PubMed] [Google Scholar]
  31. Toftgard R., Roop D. R., Yuspa S. H. Proto-oncogene expression during two-stage carcinogenesis in mouse skin. Carcinogenesis. 1985 Apr;6(4):655–657. doi: 10.1093/carcin/6.4.655. [DOI] [PubMed] [Google Scholar]
  32. Wahlberg P., Fex G., Biörklund A., Tropé C., Willén R. Quantitation and localization of cellular retinol-binding protein in squamous-cell carcinomas of the cervix uteri and of the oral cavity. Int J Cancer. 1988 May 15;41(5):771–776. doi: 10.1002/ijc.2910410523. [DOI] [PubMed] [Google Scholar]
  33. Wilhelm S. M., Collier I. E., Kronberger A., Eisen A. Z., Marmer B. L., Grant G. A., Bauer E. A., Goldberg G. I. Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6725–6729. doi: 10.1073/pnas.84.19.6725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wiseman R. W., Stowers S. J., Miller E. C., Anderson M. W., Miller J. A. Activating mutations of the c-Ha-ras protooncogene in chemically induced hepatomas of the male B6C3 F1 mouse. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5825–5829. doi: 10.1073/pnas.83.16.5825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yanagita T., Komiyama S., Kuwano M. Cellular retinol-binding proteins in head and neck tumors and their adjacent tissues. Cancer. 1986 Nov 15;58(10):2251–2255. doi: 10.1002/1097-0142(19861115)58:10<2251::aid-cncr2820581015>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  36. You M., Candrian U., Maronpot R. R., Stoner G. D., Anderson M. W. Activation of the Ki-ras protooncogene in spontaneously occurring and chemically induced lung tumors of the strain A mouse. Proc Natl Acad Sci U S A. 1989 May;86(9):3070–3074. doi: 10.1073/pnas.86.9.3070. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES