Hormonal Regulation of the EGF/Receptor System

  • Stephen W. Spaulding
  • Lowell G. Sheflin
Part of the Endocrine Updates book series (ENDO, volume 16)

Abstract

The EGF/receptor system is involved in the development, maintenance and repair of various organs, particularly those involving ductal systems. Disruptions of the EGF/receptor system have been implicated in a variety of clinical disorders including cancer and aging. Some hormones alter the expression of EGF ligands, EGF receptors and of downstream factors that mediate EGF receptor action during development. These hormonal effects vary according to the species, organ and stage of development under study. Androgens alter EGF mRNA levels in several rodent tissues, yet no androgen-responsiveness is detectable within 7 kB upstream of the promoter of the EGF gene, which supports earlier evidence that androgens have post-transcriptional actions on EGF expression. AU-rich elements that can influence transcript stability and subcellular localization are present in the 3’ UTR of EGF mRNA. Androgens regulate EGF mRNA polyadenylation site usage, poly-A tail length and mRNA stability in the mouse submaxillary salivary gland (SMG) but not in the kidney, although androgens do regulate other genes in the kidney. Androgens also regulate the levels of several AU-rich RNA binding proteins known to affect the subcellular localization, translation and stability of AU-rich mRNAs. Androgen-dependent changes in the subcellular levels of these RNA binding proteins also indicate a causal connection with the androgen-dependent changes in EGF mRNA and its translation.

Keywords

Epidermal Growth Factor Receptor Granular Convoluted Tubule Granular Convoluted Tubule Cell Epidermal Growth Factor Gene AUFI Isoforms 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Singh B., J.M. Rutledge, D.T. Armstrong: 1995, Epidermal growth factor and its receptor gene expression and peptide localization in porcine ovarian follicles, Mol Reprod Dev 40: 391–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Vaughan T.J., P.S. James, J.C. Pascall, K.D. Brown: 1992, Expression of the genes for TGF alpha, EGF and the EGF receptor during early pig development, Development 116: 663–9.PubMedGoogle Scholar
  3. 3.
    Tong B.J., S.K. Das, D. Threadgill, T. Magnuson, S.K. Dey: 1996, Differential expression of the full-length and truncated forms of the epidermal growth factor receptor in the preimplantation mouse uterus and blastocyst, Endocrinology 137: 1492–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Kliem A., F. Tetens, H. Niemann, B. Fischer: 1998, Only a truncated epidermal growth factor receptor protein is present in porcine endometrium, Biol Reprod 58: 1367–71.PubMedCrossRefGoogle Scholar
  5. 5.
    Threadgill D.W., A.A. Dlugosz, L.A. Hansen, T. Tennenbaum, U. Lichti, D. Yee, C. LaMantia, T. Mourton, K. Herrup K, R.C. Harris:1995, Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype, Science 269: 230–4, 1995.PubMedCrossRefGoogle Scholar
  6. 6.
    Chailler P., N. Briere: 1998, Mitogenic effects of EGF/TGF alpha and immunolocalization of cognate receptors in human fetal kidneys, Biofactors 7: 323–35.PubMedCrossRefGoogle Scholar
  7. 7.
    Cybulsky A.V., P.R. Goodyer, A.J. McTavish: 1994, Epidermal growth factor receptor activation in developing rat kidney, Am JPhysiol 267: F428–36.Google Scholar
  8. 8.
    North D. J. Lakshmanan, A. Reviczky, M. Kaser, D.A. Fisher: 1992, Ontogeny of epidermal growth factor, transforming growth factor-alpha, epidermal growth factor receptor, and thyroid hormone receptor RNA levels in rat kidney and changes in those levels induced by early thyroxine treatment, Pediatr Res 31: 330–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Brown M.J., G.S. Schultz, F.K. Hilton: 1984, Intrauterine proximity to male fetuses predetermines level of epidermal growth factor in submandibular glands of adult female mice. Endocrinology 115: 2318–23.PubMedCrossRefGoogle Scholar
  10. 10.
    Jaskoll T., M. Melnick: 1999, Submandibular gland morphogenesis: stage-specific expression of TGF-alpha/EGF, IGF, TGF-beta, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations, Anat Rec 256: 252–68.PubMedCrossRefGoogle Scholar
  11. 11.
    Gattone V.H. 2d, D.A. Sherman, D.A. Hinton, F.W. Niu, R.T. Topham, R.M. Klein: 1992, Epidermal growth factor in the neonatal mouse salivary gland and kidney, Biol Neonate 61: 54–67.PubMedGoogle Scholar
  12. 12.
    Salido E.C., J. Lakshmanan, S. Koy, L. Barajas, D.A. Fisher: 1990, Effect of thyroxine administration on the expression of epidermal growth factor in the kidney and submandibular gland of neonatal mice. An immunocytochemical and in situ hybridization study Endocrinology 127: 2263–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Fujieda M., Y. Murata, H. Hayashi, F. Kambe, N. Matsui, H. Seo: 1993, Effect of thyroid hormone on epidermal growth factor gene expression in mouse submandibular gland, Endocrinology 132: 121–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Kyakumoto S., R. Kurokawa, M. Ota: 1985, Effect of castration and administration of testosterone on cytosol and nuclear androgen receptor in mouse submandibular gland, Biochem Int 11: 701–7.Google Scholar
  15. 15.
    Fowler K.J., F. Walker, W. Alexander, M.L. Hibbs, E.C. Nice, R.M. Bohmer, G.B. Mann, C. Thumwood, R. Maglitto, J.A. Danks: 1995, A mutation in the epidermal growth factor receptor in waved-2 mice has a profound effect on receptor biochemistry that results in impaired lactation, Proc Natl Acad Sci U S A 92: 146–59.CrossRefGoogle Scholar
  16. 16.
    Keegan B.P., L.G. Sheflin, S.W. Spaulding: 2000, The internalization and endosomal trafficking of the EGF receptor in response to EGF is delayed in the waved-2 mouse liver, Biochem Biophys Res Commun 267: 881–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Chen B., R.T. Bronson, L.D. Klaman, T.G. Hampton, J.F. Wang, P.J. Green, T. Magnuson, P.S. Douglas, J.P.Morgan, P.G. Neel: 2000, Mice mutant for Egfr and Shpt have defective cardiac semilunar valvulogenesis, Nat Genet 24: 296–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Sebastian J., R.G. Richards, M.P. Walker, J.F. Wiesen, Z. Werb, R. Derynck, Y.K. Hom, G.R. Cunha, R.P. DiAugustine:1998, Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis, Cell Growth Differ 9: 777–85.Google Scholar
  19. 19.
    Luetteke N.C., T.h. Qiu, S.E Fenton, K.L. Troyer, R.F. Riedel, A. Chang, D.C. Lee:1999, Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development, Development 126: 2739–50.Google Scholar
  20. 20.
    Fenton S.E., N.S. Groce, D.C. Lee: 1996, Characterization of the mouse epidermal growth factor promoter and 5’-flanking region. Role for an atypical TATA sequence, JBiol Chem 271: 30870–8, 1996.Google Scholar
  21. 21.
    Sheflin L.G., E.M. Brooks, B.P. Keegan, S.W. Spaulding: 1996, Increased epidermal growth factor expression produced by testosterone in the submaxillary gland of female mice is accompanied by changes in poly-A tail length and periodicity, Endocrinology 137: 2085–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Sheflin L.G., E.M. Brooks, S.W. Spaulding: 1996, Testosterone regulates tissue-specific changes in the binding of a 47-kilodalton protein to a highly conserved sequence in the 3’ untranslated region of epidermal growth factor messenger ribonucleic acid, Endocrinology 137: 2910–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Sheflin L.G., E.M. Brooks, B.P. Keegan, S.W. Spaulding: 1996, The cytosolic 47kilodalton protein that binds to the 3’ untranslated region of epidermal growth factor transcripts responds to orchiectomy in a tissue-specific fashion, Endocrinology 137: 5616–23.PubMedCrossRefGoogle Scholar
  24. 24.
    Pascall J.C.: 1997, Post-transcriptional regulation of gene expression by androgens-recent observations from the epidermal growth factor gene, J Mol Endocrinol 18: 177–80.PubMedCrossRefGoogle Scholar
  25. 25.
    Qian J.F., E. Lazar-Wesley, C. Breugnot, E. May: 1993, Human transforming growth factor alpha: sequence analysis of the 4.5-kb and 1.6-kb mRNA species, Gene 132: 291–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Berkowitz E.A., Hissong MA, Lee DC: 1996, Transcriptional and post-transcriptional induction of the TGF alpha gene in transformed rat liver epithelial cells, Oncogene 12: 1991–2002.PubMedGoogle Scholar
  27. 27.
    Gaido K.W., S.C.Maness, L.S. Leonard, W.F. Greenlee 1992, 2,3,7,8-Tetrachlorodibenzo-p-dioxin-dependent regulation of transforming growth factors-alpha and -beta 2 expression in a human keratinocyte cell line involves both transcriptional and post-transcriptional control, JBiol Chem 267: 24591–5.Google Scholar
  28. 28.
    Nicolini G., M. Miloso, M.C. Moroni, L. Beguinot, L. Scotto: 1996, Post-transcriptional control regulates transforming growth factor alpha in the human carcinoma KB cell line, JBiol Chem 271: 30290–6.CrossRefGoogle Scholar
  29. 29.
    Satoh Y., M. Oomae, Y. Hoshikawa, M. Izawa, T. Sairenji, S. Ichii: 1997, The stability of truncated epidermal growth factor receptor mRNA is higher than that of the full-length receptor mRNA in rat hepatoma cells. Endocr J44: 403–8.CrossRefGoogle Scholar
  30. 30.
    McCulloch R.K., C.E. Walker, A. Chakera, J. Jazayeri, P.J. Leedman: 1998, Regulation of EGF-receptor expression by EGF and TGF alpha in epidermoid cancer cells is cell type-specific, Int J Biochem Cell Biol 30: 1265–78.PubMedCrossRefGoogle Scholar
  31. 31.
    Kesavan P., S. Mukhopadhayay, S. Murphy, M. Rengaraju, M.A. Lazar, M. Das: 1991, Thyroid hormone decreases the expression of epidermal growth factor receptor, J Biol Chem 266: 10282–6.PubMedGoogle Scholar
  32. 32.
    Brooks E.M., L.G. Sheflin, S.W. Spaulding: 1995, Secondary structure in the 3’ UTR of EGF and the choice of reverse transcriptases affect the detection of message diversity by RT-PCR, Biotechniques 19: 806–15.PubMedGoogle Scholar
  33. 33.
    Sheflin L.G., E.M. Brooks, S.W. Spaulding: 1995, Assessment of transcript polyadenylation by 3’ RACE: the response of epidermal growth factor messenger ribonucleic acid to thyroid hormone in the thyroid and submaxillary glands, Endocrinology 136: 5666–76.PubMedCrossRefGoogle Scholar
  34. 34.
    Carter D.A. D. Murphy: 1993, Regulation of vasopressin (VP) gene expression in the bed nucleus of the stria terminalis: gonadal steroid-dependent changes in VP mRNA accumulation are associated with alterations in mRNA poly (A) tail length but are independent of the rate of VP gene transcription, J Neuroendocrinol 5: 509–15.PubMedCrossRefGoogle Scholar
  35. 35.
    Vercaeren I., J. Winderickx, A. Devos, B. Peeters, W. Heyns: 1992, An effect of androgens on the length of the poly(A)-tail and alternative splicing cause size heterogeneity of the messenger ribonucleic acids encoding cystatin-related protein, Endocrinology 131: 2496–502.Google Scholar
  36. 36.
    Wagner B.J., C.T. DeMaria, Y. Sun Y, G.M. Wilson, G. Brewer: 1998, Structure and genomic organization of the human AUF1 gene: alternative pre-mRNA splicing generates four protein isoforms, Genomics 48: 195–202.Google Scholar
  37. 37.
    Dreyfuss G., M.J. Matunis, S. Pinol-Roma, G.C. Burd: 1993, hnRNP proteins and the biogenesis of mRNA, Annu Rev Biochem 62: 289–321.Google Scholar
  38. 38.
    Bhattacharya S., T. Giordano, G. Brewer, J.S. Malter: 1999, Identification of AUF-1 ligands reveals vast diversity of early response gene mRNAs. Identification of AUF-1 ligands reveals vast diversity of early response gene mRNAs, Nucleic Acids Res 27: 1464–72.PubMedCrossRefGoogle Scholar
  39. 39.
    Zhao Z., F.C. Chang, H.M. Furneaux: 2000, The identification of an endonuclease that cleaves within an HuR binding site in mRNA. Nucleic Acids Res 28: 2695–701.PubMedCrossRefGoogle Scholar
  40. 40.
    Pende A., K.D. Tremmel, C.T. DeMaria, B.C. Blaxall, W.A. Minobe, J.A. Sherman, J.D. Bisognano, Bristow, G. Brewer, J.D. Port JD: 1996, Regulation of the mRNA-binding protein AUF1 by activation of the beta-adrenergic receptor signal transduction pathway, J Biol Chem 271: 8493–501.Google Scholar
  41. 41.
    Loflin P., C.Y. Chen, A.B. Shyu: 1999, Unraveling a cytoplasmic role for hnRNP D in the in vivo mRNA destabilization directed by the AU-rich element, Genes Dev 13: 1884–97.PubMedCrossRefGoogle Scholar
  42. 42.
    Laroia G., R.G. Cuesta, G. Brewer, R.J. Schneider: 1999, Control of mRNA decay by heat shock-ubiquitin-proteasome pathway, Science, 284: 499–502.PubMedCrossRefGoogle Scholar
  43. 43.
    Sheflin LG, S.W. Spaulding: 2000, Testosterone and dihydrotestosterone regulate AUF1 isoforms in a tissue-specific fashion in the mouse, Am J Physiol Endocrinol Metab 278:E50–7Google Scholar
  44. 44.
    Scheflin L.G., W. Zhang, S.W. Spaulding. 2001, Androgen regulates the level and subcellular distribution of the AU-rich RNA binding protein HuR both in vivo and in vitro. Endocrinology 142: 2361–2368.CrossRefGoogle Scholar
  45. 45.
    Sela-Brown A,. J. Silver, G. Brewer, T. Naveh-Many: 2000, Identification of AUF1 as a parathyroid hormone mRNA 3’-untranslated region-binding protein that determines parathyroid hormone mRNA stability, JBiol Chem 275: 7424–9.CrossRefGoogle Scholar
  46. 46.
    Blaxall B.C., A.C. Pellet, S.C., Wu SC, A. Pende, J.D. Port: 2000, Purification and characterization of beta-adrenergic receptor mRNA-binding proteins, J Biol Chem 275: 4290–7.Google Scholar
  47. 47.
    Arao Y., R. Kuriyama, F. Kayama, S Kato: 2000, A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D, Arch Biochem Biophys 380:228–36. mouse kidney is posttranscriptional, Biochemistry 25: 1170–5.Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Stephen W. Spaulding
    • 1
  • Lowell G. Sheflin
    • 1
  1. 1.VA Western New York and SUNY at BuffaloBuffaloUSA

Personalised recommendations