Summary
Recent advances in the molecular action of steroid hormones and in the role of oncogenes in cell transformation are considered in defining, at the molecular level, the involvement of steroid hormones in tumour formation. In the context of the generally accepted three-stage model of carcinogenesis, it is proposed that the hormonal steroids act as tumour promoters by modulating oncogene expression. It is postulated that the hormonal steroids act on cells in which the initiating carcinogen has either induced mutations in protooncogenes normally hormonally regulated or has induced changes in gene architecture, aligning protooncogenes to hormone-responsive elements, thus placing these genes under nonphysiological hormonal control. In contrast to the defined action of solitary carcinogens on the genetic material, tumour promoters appear to act by various molecular pathways, one of which, as hypothesized for hormonal steroids, could be a direct effect on oncogene expression.
This is a preview of subscription content, log in via an institution to check access.
References
Beato M, Chalepakis G, Schauer M, Slater EP (1989) DNA regulatory elements for steroid hormones. J Steroid Biochem 32:737–748
Beatson GT (1896) On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases. Lancet 11:104–107
Bouchard L, Lilamarre L, Tremblay PJ, Jolicoeur P (1989) Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene. Cell 57:931–936
de Braekeller M (1988) Proto-oncogenes, growth factor genes, receptor genes, differentiation genes and structural rearrangements in human cancer. Anticancer Res 8:1325–1328
Butenandt A (1950) Zur physiologischen Bedeutung des Follikelhormons und der östrogenen Wirkstoffe für die Genese des Brustdrüsenkrebses und die Therapie des Prostata-Karzinoms. Dtsch Med Wochenschr 75:5–7
Chorazy M (1985) Sequence rearrangements and genome instability —a possible step in carcinogenesis. J Cancer Res Clin Oncol 109:159–172
Dunning WF, Curtis MR, Segaloff A (1947) Strain differences in response to diethylstilbestrol and the induction of mammary gland and bladder cancer in the rat. Cancer Res 7:511–521
Evans RM (1988) The steroid and thyroid hormone receptor super-family. Science 240:889–895
Green S, Chambon P (1988) Nuclear receptors enhance our understanding of transcription regulation. Trends Genet 4:309–314
Hecker E (1978) Co-carcinogene oder bedingt krebsauslösende Faktoren. Naturwissenschaften 65:640–648
Hecker E (1987) Three stage carcinogenesis in house skin — recent results and present status of an advanced model system of chemical carcinogenesis. Toxicol Pathol 15:245–258
Hudziak RM, Schlessinger J, Ullrich A (1987) Increased expression of the putative growth factor receptor p185 HER2 causes transformation and tumorigenesis of NIH 313 cells. Proc Natl Acad Sci USA 84:7159–7163
Huggins C, Hodges CV (1941) Studies on prostatic cancer. I. The effect of castration of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1:293–297
Huggins C, Stevens RE, Hodges CV (1941) Studies on prostate cancer. II. The effect of castration on advanced carcinoma of the prostate gland. Arch Surg 43:209–223
Huggins C, Briziarelli G, Sutton H (1959) Rapid induction of mammary carcinoma in the rat and the influence of hormones on the tumors. J Exp Med 109:25–41
Huggins C, Grand LC, Brillantes FP (1961) Mammary cancer induced by a single feeding of polynuclear hydrocarbons and its suppression. Nature 189:204–207
Karlson P (1961) Biochemische Wirkungsweise der Hormone. Dtsch Med Wochenschr 86:668–674
Kaufmann C, Aurel Müller H, Butenandt A, Friedrich-Freska H (1949) Experimentelle Beiträge zur Bedeutung des Folikelhormons für die Carcinomentstehung. Z Krebsforsch 56:482–542
Loose-Mitchel DS, Chiappetta C, Stancel GM (1988) Estrogen regulation of c-fos messenger ribonucleic acid. Mol Endocrinol 2:946–951
Markham PD, Salahuddin SZ, Veren K, Orndorff S, Gallo RC (1986) Hydrocortisone and some other hormones enhance the expression of HTLV-III. Int J Cancer 37:67–72
Miksicek R, Heber A, Schmid W, Danesch U, Posseckert G, Beato M, Schütz G (1986) Glucocorticoid responsiveness of the transcriptional enhancer of maloney murine sarcoma virus. Cell 46:283–290
Müller WJ, Sinn E, Pattengale PK, Wallace R, Leder P (1988) Single step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene Cell 54:105–115
Papter MM, Hughes GA, Hyslop DE, Nakshatu H, Pater A (1988) Glucocorticoid dependent oncogenic transformation by type 16 but not type II human papilloma viurs DNA. Nature 335:832–835
Peters G, Brookes S, Smith R, Dickson C (1983) Tumorigenesis by mouse mammary tumor virus: evidence for a common region for provirus integration in mammary tumors. Cell 33:369–377
Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF (1989) Studies of the HER-2/neu protooncogene in human breast and ovarian cancer. Science 244:707–712
Soule HD, Vasquez J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409–1413
Spandidos DA, Zoumpourlis V, Kotsinas A, Tsiriyotis C, Sekeris CE (1990) Response of human immunodeficiency virus long terminal repeat to growth factors and hormones. Anticaner Res 10:1241–1246
Stavenhagen JB, Robins DM (1988) An ancient provirus has imposed androgen regulation on the adjacent mouse sex-limited protein gene. Cell 55:247–254
Weinberg RA (1985) The action of oncogenes in the cytoplasm and nucleus. Science 230:770–776
Weisz A, Bresciani F (1988) Estrogen induces expression of c-fos and c-myc protooncogenes in rat uterus. Mol Endocrinol 2:816–824
Author information
Authors and Affiliations
Additional information
This paper is gratefully dedicated to Professor A. Butenandt on the occasion of his 88 th birthday
The “Journal of Cancer Research and Clinical Oncology” publishes in loose succession “Editorials” and “Guest editorials” on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author The Editors
Rights and permissions
About this article
Cite this article
Sekeris, E. Hormonal steroids act as tumour promoters by modulating oncogene expression. J Cancer Res Clin Oncol 117, 96–101 (1991). https://doi.org/10.1007/BF01613131
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01613131