Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;75(2):251–257. doi: 10.1038/bjc.1997.41

Type I insulin-like growth factor receptor gene expression in normal human breast tissue treated with oestrogen and progesterone.

R B Clarke 1, A Howell 1, E Anderson 1
PMCID: PMC2063278  PMID: 9010034

Abstract

The epithelial proliferation of normal human breast tissue xenografts implanted into athymic nude mice is significantly increased from basal levels by oestradiol (E2), but not progesterone (Pg) treatment at serum concentrations similar to those observed in the luteal phase of the human menstrual cycle. Type I IGF receptor (IGFR-I) mRNA and protein have been shown to be up-regulated by E2 in MCF-7 breast cancer cells in vitro in which IGF-I and E2 act synergistically to stimulate proliferation. We have investigated the expression of the IGFR-I mRNA in normal human breast xenografts treated with or without E2 or Pg alone and in combination. Northern analysis of 20 micrograms of RNA extracted from the breast xenograft samples showed no hybridization with 32P-labelled IGFR-I probe, although an 11-kb species of IGFR-I mRNA could be seen when 20 micrograms of RNA extracted from either MCF-7 breast cancer cells or human breast carcinomas was examined in this way. In order to analyse the expression of IGFR-I mRNA in breast xenografts, a quantitative reverse transcription-polymerase chain reaction (RT-PCR) was employed in which RNA loading, reverse transcription and PCR efficiencies were internally controlled. The data indicate that the IGFR-I mRNA is up-regulated by two to threefold compared with untreated levels by 7 and 14 days E2 treatment. In contrast, 7 or 14 days Pg treatment down-regulates the receptor mRNA to approximately half that of untreated levels, whereas combination E2 and Pg treatment produced a twofold increase in IGFR-I mRNA levels compared with untreated tissue. The results are consistent with the suggestion that E2 may act to stimulate proliferation indirectly via a paracrine mechanism involving IGFs in normal as well as malignant human breast epithelial cells.

Full text

PDF
254

Selected References

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

  1. Arteaga C. L., Kitten L. J., Coronado E. B., Jacobs S., Kull F. C., Jr, Allred D. C., Osborne C. K. Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice. J Clin Invest. 1989 Nov;84(5):1418–1423. doi: 10.1172/JCI114315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Becker-André M., Hahlbrock K. Absolute mRNA quantification using the polymerase chain reaction (PCR). A novel approach by a PCR aided transcript titration assay (PATTY). Nucleic Acids Res. 1989 Nov 25;17(22):9437–9446. doi: 10.1093/nar/17.22.9437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bronzert D. A., Pantazis P., Antoniades H. N., Kasid A., Davidson N., Dickson R. B., Lippman M. E. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5763–5767. doi: 10.1073/pnas.84.16.5763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brünner N., Yee D., Kern F. G., Spang-Thomsen M., Lippman M. E., Cullen K. J. Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II). Eur J Cancer. 1993;29A(4):562–569. doi: 10.1016/s0959-8049(05)80152-2. [DOI] [PubMed] [Google Scholar]
  5. Clemmons D. R., Van Wyk J. J. Factors controlling blood concentration of somatomedin C. Clin Endocrinol Metab. 1984 Mar;13(1):113–143. doi: 10.1016/s0300-595x(84)80011-0. [DOI] [PubMed] [Google Scholar]
  6. Cullen K. J., Smith H. S., Hill S., Rosen N., Lippman M. E. Growth factor messenger RNA expression by human breast fibroblasts from benign and malignant lesions. Cancer Res. 1991 Sep 15;51(18):4978–4985. [PubMed] [Google Scholar]
  7. Cullen K. J., Yee D., Rosen N. Insulinlike growth factors in human malignancy. Cancer Invest. 1991;9(4):443–454. doi: 10.3109/07357909109084643. [DOI] [PubMed] [Google Scholar]
  8. Cullen K. J., Yee D., Sly W. S., Perdue J., Hampton B., Lippman M. E., Rosen N. Insulin-like growth factor receptor expression and function in human breast cancer. Cancer Res. 1990 Jan 1;50(1):48–53. [PubMed] [Google Scholar]
  9. Daughaday W. H., Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev. 1989 Feb;10(1):68–91. doi: 10.1210/edrv-10-1-68. [DOI] [PubMed] [Google Scholar]
  10. Gabelman B. M., Emerman J. T. Effects of estrogen, epidermal growth factor, and transforming growth factor-alpha on the growth of human breast epithelial cells in primary culture. Exp Cell Res. 1992 Jul;201(1):113–118. doi: 10.1016/0014-4827(92)90354-b. [DOI] [PubMed] [Google Scholar]
  11. Ghahary A., Murphy L. J. Uterine insulin-like growth factor-I receptors: regulation by estrogen and variation throughout the estrous cycle. Endocrinology. 1989 Aug;125(2):597–604. doi: 10.1210/endo-125-2-597. [DOI] [PubMed] [Google Scholar]
  12. Gilliland G., Perrin S., Blanchard K., Bunn H. F. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2725–2729. doi: 10.1073/pnas.87.7.2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gompel A., Malet C., Spritzer P., Lalardrie J. P., Kuttenn F., Mauvais-Jarvis P. Progestin effect on cell proliferation and 17 beta-hydroxysteroid dehydrogenase activity in normal human breast cells in culture. J Clin Endocrinol Metab. 1986 Nov;63(5):1174–1180. doi: 10.1210/jcem-63-5-1174. [DOI] [PubMed] [Google Scholar]
  14. Humbel R. E. Insulin-like growth factors I and II. Eur J Biochem. 1990 Jul 5;190(3):445–462. doi: 10.1111/j.1432-1033.1990.tb15595.x. [DOI] [PubMed] [Google Scholar]
  15. Jammes H., Peyrat J. P., Ban E., Vilain M. O., Haour F., Djiane J., Bonneterre J. Insulin-like growth factor 1 receptors in human breast tumour: localisation and quantification by histo-autoradiographic analysis. Br J Cancer. 1992 Aug;66(2):248–253. doi: 10.1038/bjc.1992.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Karey K. P., Sirbasku D. A. Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17 beta-estradiol. Cancer Res. 1988 Jul 15;48(14):4083–4092. [PubMed] [Google Scholar]
  17. Krowczynska A. M., Coutts M., Makrides S., Brawerman G. The mouse homologue of the human acidic ribosomal phosphoprotein PO: a highly conserved polypeptide that is under translational control. Nucleic Acids Res. 1989 Aug 11;17(15):6408–6408. doi: 10.1093/nar/17.15.6408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laborda J. 36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO. Nucleic Acids Res. 1991 Jul 25;19(14):3998–3998. doi: 10.1093/nar/19.14.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Laidlaw I. J., Clarke R. B., Howell A., Owen A. W., Potten C. S., Anderson E. The proliferation of normal human breast tissue implanted into athymic nude mice is stimulated by estrogen but not progesterone. Endocrinology. 1995 Jan;136(1):164–171. doi: 10.1210/endo.136.1.7828527. [DOI] [PubMed] [Google Scholar]
  20. Malet C., Gompel A., Spritzer P., Bricout N., Yaneva H., Mowszowicz I., Kuttenn F., Mauvais-Jarvis P. Tamoxifen and hydroxytamoxifen isomers versus estradiol effects on normal human breast cells in culture. Cancer Res. 1988 Dec 15;48(24 Pt 1):7193–7199. [PubMed] [Google Scholar]
  21. Masiakowski P., Breathnach R., Bloch J., Gannon F., Krust A., Chambon P. Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res. 1982 Dec 20;10(24):7895–7903. doi: 10.1093/nar/10.24.7895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Paik S. Expression of IGF-I and IGF-II mRNA in breast tissue. Breast Cancer Res Treat. 1992;22(1):31–38. doi: 10.1007/BF01833331. [DOI] [PubMed] [Google Scholar]
  23. Papa V., Hartmann K. K., Rosenthal S. M., Maddux B. A., Siiteri P. K., Goldfine I. D. Progestins induce down-regulation of insulin-like growth factor-I (IGF-I) receptors in human breast cancer cells: potential autocrine role of IGF-II. Mol Endocrinol. 1991 May;5(5):709–717. doi: 10.1210/mend-5-5-709. [DOI] [PubMed] [Google Scholar]
  24. Pekonen F., Partanen S., Mäkinen T., Rutanen E. M. Receptors for epidermal growth factor and insulin-like growth factor I and their relation to steroid receptors in human breast cancer. Cancer Res. 1988 Mar 1;48(5):1343–1347. [PubMed] [Google Scholar]
  25. Perusinghe N. P., Monaghan P., O'Hare M. J., Ashley S., Gusterson B. A. Effects of growth factors on proliferation on basal and luminal cells in human breast epithelial explants in serum-free culture. In Vitro Cell Dev Biol. 1992 Feb;28A(2):90–96. doi: 10.1007/BF02631011. [DOI] [PubMed] [Google Scholar]
  26. Peyrat J. P., Bonneterre J., Vennin P. H., Jammes H., Beuscart R., Hecquet B., Djiane J., Lefebvre J., Demaille A. Insulin-like growth factor 1 receptors (IGF1-R) and IGF1 in human breast tumors. J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):823–827. doi: 10.1016/0960-0760(90)90426-l. [DOI] [PubMed] [Google Scholar]
  27. Rich B. E., Steitz J. A. Human acidic ribosomal phosphoproteins P0, P1, and P2: analysis of cDNA clones, in vitro synthesis, and assembly. Mol Cell Biol. 1987 Nov;7(11):4065–4074. doi: 10.1128/mcb.7.11.4065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Richards J., Imagawa W., Balakrishnan A., Edery M., Nandi S. The lack of effect of phenol red or estradiol on the growth response of human, rat, and mouse mammary cells in primary culture. Endocrinology. 1988 Sep;123(3):1335–1340. doi: 10.1210/endo-123-3-1335. [DOI] [PubMed] [Google Scholar]
  29. Ruan W., Catanese V., Wieczorek R., Feldman M., Kleinberg D. L. Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid. Endocrinology. 1995 Mar;136(3):1296–1302. doi: 10.1210/endo.136.3.7867584. [DOI] [PubMed] [Google Scholar]
  30. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stewart A. J., Johnson M. D., May F. E., Westley B. R. Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. J Biol Chem. 1990 Dec 5;265(34):21172–21178. [PubMed] [Google Scholar]
  32. Stewart J. P., Behm F. G., Arrand J. R., Rooney C. M. Differential expression of viral and human interleukin-10 (IL-10) by primary B cell tumors and B cell lines. Virology. 1994 May 1;200(2):724–732. doi: 10.1006/viro.1994.1236. [DOI] [PubMed] [Google Scholar]
  33. Thorsen T., Lahooti H., Rasmussen M., Aakvaag A. Oestradiol treatment increases the sensitivity of MCF-7 cells for the growth stimulatory effect of IGF-I. J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):537–540. doi: 10.1016/0960-0760(92)90379-w. [DOI] [PubMed] [Google Scholar]
  34. Ullrich A. Insulin-like growth factor I receptor cDNA cloning. Methods Enzymol. 1991;198:17–26. doi: 10.1016/0076-6879(91)98004-p. [DOI] [PubMed] [Google Scholar]
  35. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  36. Wang A. M., Doyle M. V., Mark D. F. Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9717–9721. doi: 10.1073/pnas.86.24.9717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yee D., Paik S., Lebovic G. S., Marcus R. R., Favoni R. E., Cullen K. J., Lippman M. E., Rosen N. Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer. Mol Endocrinol. 1989 Mar;3(3):509–517. doi: 10.1210/mend-3-3-509. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES