Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jan 1;88(1):276–280. doi: 10.1073/pnas.88.1.276

Expression and functional properties of transforming growth factor alpha and epidermal growth factor during mouse mammary gland ductal morphogenesis.

S M Snedeker 1, C F Brown 1, R P DiAugustine 1
PMCID: PMC50793  PMID: 1986376

Abstract

Primer-directed enzyme amplification was used to examine epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) mRNA transcripts in mammary glands of young virgin, mature virgin, midpregnant, and midlactating mice. Transcripts for both EGF and TGF-alpha mRNA were detected in virgin and pregnant mice, whereas transcripts for EGF mRNA but not TGF-alpha mRNA were expressed in 10-day lactating mice. TGF-alpha was localized in the epithelial cap-cell layer of the advancing terminal end bud and in the stromal fibroblasts at the base of the terminal end bud; EGF was localized in the inner layers of the terminal end bud and in ductal cells of mammary epithelium. Implantation of pellets containing EGF or TGF-alpha into the regressed mammary gland of ovariectomized mice stimulated the reappearance of end buds; contralateral glands implanted with pellets containing albumin or insulin were not affected. These results indicate that an EGF-receptor-mediated pathway remained intact in the mammary gland epithelium in the absence of ovarian steroids and that local availability of either EGF or TGF-alpha is sufficient to stimulate the pattern of normal ductal growth. The detection of EGF and TFF-alpha transcripts at different stages of mammary gland development and the different patterns of immunolocalization suggest that each polypeptide plays a different role in normal mammary gland morphogenesis.

Full text

PDF
276

Images in this article

277Image
on p.277
277Image
on p.277
277Image
on p.277
278Image
on p.278
278Image
on p.278
278Image
on p.278
278Image
on p.278
279Image
on p.279
279Image
on p.279
279Image
on p.279
279Image
on p.279
279Image
on p.279
279Image
on p.279

Selected References

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

  1. Alonso S., Minty A., Bourlet Y., Buckingham M. Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates. J Mol Evol. 1986;23(1):11–22. doi: 10.1007/BF02100994. [DOI] [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BRESCIANI F. EFFECT OF OVARIAN HORMONES ON DURATION OF DNA SYNTHESIS IN CELLS OF THE C3H MOUSE MAMMARY GLAND. Exp Cell Res. 1965 Apr;38:13–32. doi: 10.1016/0014-4827(65)90423-4. [DOI] [PubMed] [Google Scholar]
  4. Bates S. E., Davidson N. E., Valverius E. M., Freter C. E., Dickson R. B., Tam J. P., Kudlow J. E., Lippman M. E., Salomon D. S. Expression of transforming growth factor alpha and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and its possible functional significance. Mol Endocrinol. 1988 Jun;2(6):543–555. doi: 10.1210/mend-2-6-543. [DOI] [PubMed] [Google Scholar]
  5. Brown C. F., Teng C. T., Pentecost B. T., DiAugustine R. P. Epidermal growth factor precursor in mouse lactating mammary gland alveolar cells. Mol Endocrinol. 1989 Jul;3(7):1077–1083. doi: 10.1210/mend-3-7-1077. [DOI] [PubMed] [Google Scholar]
  6. Carpenter G. Epidermal growth factor is a major growth-promoting agent in human milk. Science. 1980 Oct 10;210(4466):198–199. doi: 10.1126/science.6968093. [DOI] [PubMed] [Google Scholar]
  7. Chen L. B., Gudor R. C., Sun T. T., Chen A. B., Mosesson M. W. Control of a cell surface major glycoprotein by epidermal growth factor. Science. 1977 Aug 19;197(4305):776–778. doi: 10.1126/science.302030. [DOI] [PubMed] [Google Scholar]
  8. Clark A. J., Ishii S., Richert N., Merlino G. T., Pastan I. Epidermal growth factor regulates the expression of its own receptor. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8374–8378. doi: 10.1073/pnas.82.24.8374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coffey R. J., Jr, Derynck R., Wilcox J. N., Bringman T. S., Goustin A. S., Moses H. L., Pittelkow M. R. Production and auto-induction of transforming growth factor-alpha in human keratinocytes. 1987 Aug 27-Sep 2Nature. 328(6133):817–820. doi: 10.1038/328817a0. [DOI] [PubMed] [Google Scholar]
  10. Coleman S., Silberstein G. B., Daniel C. W. Ductal morphogenesis in the mouse mammary gland: evidence supporting a role for epidermal growth factor. Dev Biol. 1988 Jun;127(2):304–315. doi: 10.1016/0012-1606(88)90317-x. [DOI] [PubMed] [Google Scholar]
  11. Daniel C. W., Silberstein G. B., Strickland P. Direct action of 17 beta-estradiol on mouse mammary ducts analyzed by sustained release implants and steroid autoradiography. Cancer Res. 1987 Nov 15;47(22):6052–6057. [PubMed] [Google Scholar]
  12. Derynck R., Goeddel D. V., Ullrich A., Gutterman J. U., Williams R. D., Bringman T. S., Berger W. H. Synthesis of messenger RNAs for transforming growth factors alpha and beta and the epidermal growth factor receptor by human tumors. Cancer Res. 1987 Feb 1;47(3):707–712. [PubMed] [Google Scholar]
  13. Derynck R., Roberts A. B., Winkler M. E., Chen E. Y., Goeddel D. V. Human transforming growth factor-alpha: precursor structure and expression in E. coli. Cell. 1984 Aug;38(1):287–297. doi: 10.1016/0092-8674(84)90550-6. [DOI] [PubMed] [Google Scholar]
  14. DiAugustine R. P., Petrusz P., Bell G. I., Brown C. F., Korach K. S., McLachlan J. A., Teng C. T. Influence of estrogens on mouse uterine epidermal growth factor precursor protein and messenger ribonucleic acid. Endocrinology. 1988 Jun;122(6):2355–2363. doi: 10.1210/endo-122-6-2355. [DOI] [PubMed] [Google Scholar]
  15. Dickson R. B., Huff K. K., Spencer E. M., Lippman M. E. Induction of epidermal growth factor-related polypeptides by 17 beta-estradiol in MCF-7 human breast cancer cells. Endocrinology. 1986 Jan;118(1):138–142. doi: 10.1210/endo-118-1-138. [DOI] [PubMed] [Google Scholar]
  16. Dulbecco R., Henahan M., Armstrong B. Cell types and morphogenesis in the mammary gland. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7346–7350. doi: 10.1073/pnas.79.23.7346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. FAULKIN L. J., Jr, DEOME K. B. Regulation of growth and spacing of gland elements in the mammary fat pad of the C3H mouse. J Natl Cancer Inst. 1960 Apr;24:953–969. [PubMed] [Google Scholar]
  18. Green J., Muallem S. A common mechanism for activation of the Na+/H+ exchanger by different types of stimuli. FASEB J. 1989 Oct;3(12):2408–2414. doi: 10.1096/fasebj.3.12.2551762. [DOI] [PubMed] [Google Scholar]
  19. Han J. H., Stratowa C., Rutter W. J. Isolation of full-length putative rat lysophospholipase cDNA using improved methods for mRNA isolation and cDNA cloning. Biochemistry. 1987 Mar 24;26(6):1617–1625. doi: 10.1021/bi00380a020. [DOI] [PubMed] [Google Scholar]
  20. Haslam S. Z. Mammary fibroblast influence on normal mouse mammary epithelial cell responses to estrogen in vitro. Cancer Res. 1986 Jan;46(1):310–316. [PubMed] [Google Scholar]
  21. Imagawa W., Tomooka Y., Hamamoto S., Nandi S. Stimulation of mammary epithelial cell growth in vitro: interaction of epidermal growth factor and mammogenic hormones. Endocrinology. 1985 Apr;116(4):1514–1524. doi: 10.1210/endo-116-4-1514. [DOI] [PubMed] [Google Scholar]
  22. Lee D. C., Rochford R., Todaro G. J., Villarreal L. P. Developmental expression of rat transforming growth factor-alpha mRNA. Mol Cell Biol. 1985 Dec;5(12):3644–3646. doi: 10.1128/mcb.5.12.3644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee D. C., Rose T. M., Webb N. R., Todaro G. J. Cloning and sequence analysis of a cDNA for rat transforming growth factor-alpha. Nature. 1985 Feb 7;313(6002):489–491. doi: 10.1038/313489a0. [DOI] [PubMed] [Google Scholar]
  24. Lembach K. J. Enhanced synthesis and extracellular accumulation of hyaluronic acid during stimulation of quiescent human fibroblasts by mouse epidermal growth factor. J Cell Physiol. 1976 Oct;89(2):277–288. doi: 10.1002/jcp.1040890211. [DOI] [PubMed] [Google Scholar]
  25. Lippman M. E., Dickson R. B., Kasid A., Gelmann E., Davidson N., McManaway M., Huff K., Bronzert D., Bates S., Swain S. Autocrine and paracrine growth regulation of human breast cancer. J Steroid Biochem. 1986 Jan;24(1):147–154. doi: 10.1016/0022-4731(86)90044-0. [DOI] [PubMed] [Google Scholar]
  26. Liscia D. S., Merlo G., Ciardiello F., Kim N., Smith G. H., Callahan R., Salomon D. S. Transforming growth factor-alpha messenger RNA localization in the developing adult rat and human mammary gland by in situ hybridization. Dev Biol. 1990 Jul;140(1):123–131. doi: 10.1016/0012-1606(90)90059-r. [DOI] [PubMed] [Google Scholar]
  27. Liu S. C., Sanfilippo B., Perroteau I., Derynck R., Salomon D. S., Kidwell W. R. Expression of transforming growth factor alpha (TGF alpha) in differentiated rat mammary tumors: estrogen induction of TGF alpha production. Mol Endocrinol. 1987 Oct;1(10):683–692. doi: 10.1210/mend-1-10-683. [DOI] [PubMed] [Google Scholar]
  28. Malden L. T., Novak U., Burgess A. W. Expression of transforming growth factor alpha messenger RNA in the normal and neoplastic gastro-intestinal tract. Int J Cancer. 1989 Mar 15;43(3):380–384. doi: 10.1002/ijc.2910430305. [DOI] [PubMed] [Google Scholar]
  29. Marquardt H., Hunkapiller M. W., Hood L. E., Todaro G. J. Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science. 1984 Mar 9;223(4640):1079–1082. doi: 10.1126/science.6320373. [DOI] [PubMed] [Google Scholar]
  30. McGrath C. M. Augmentation of the response of normal mammary epithelial cells to estradiol by mammary stroma. Cancer Res. 1983 Mar;43(3):1355–1360. [PubMed] [Google Scholar]
  31. Murray J. B., Brown L., Langer R., Klagsburn M. A micro sustained release system for epidermal growth factor. In Vitro. 1983 Oct;19(10):743–748. doi: 10.1007/BF02618093. [DOI] [PubMed] [Google Scholar]
  32. NANDI S. Endocrine control of mammarygland development and function in the C3H/ He Crgl mouse. J Natl Cancer Inst. 1958 Dec;21(6):1039–1063. [PubMed] [Google Scholar]
  33. Nanney L. B., McKanna J. A., Stoscheck C. M., Carpenter G., King L. E. Visualization of epidermal growth factor receptors in human epidermis. J Invest Dermatol. 1984 Feb;82(2):165–169. doi: 10.1111/1523-1747.ep12259731. [DOI] [PubMed] [Google Scholar]
  34. Ordronneau P., Lindström P. B., Petrusz P. Four unlabeled antibody bridge techniques: a comparison. J Histochem Cytochem. 1981 Dec;29(12):1397–1404. doi: 10.1177/29.12.7033366. [DOI] [PubMed] [Google Scholar]
  35. Perroteau I., Salomon D., DeBortoli M., Kidwell W., Hazarika P., Pardue R., Dedman J., Tam J. Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells. Breast Cancer Res Treat. 1986;7(3):201–210. doi: 10.1007/BF01806251. [DOI] [PubMed] [Google Scholar]
  36. Rall L. B., Scott J., Bell G. I., Crawford R. J., Penschow J. D., Niall H. D., Coghlan J. P. Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues. Nature. 1985 Jan 17;313(5999):228–231. doi: 10.1038/313228a0. [DOI] [PubMed] [Google Scholar]
  37. Rappolee D. A., Brenner C. A., Schultz R., Mark D., Werb Z. Developmental expression of PDGF, TGF-alpha, and TGF-beta genes in preimplantation mouse embryos. Science. 1988 Sep 30;241(4874):1823–1825. doi: 10.1126/science.3175624. [DOI] [PubMed] [Google Scholar]
  38. Richards J. E., Shyamala G., Nandi S. Estrogen receptor in normal and neoplastic mouse mammary tissues. Cancer Res. 1974 Oct;34(10):2764–2772. [PubMed] [Google Scholar]
  39. Richards J., Guzman R., Konrad M., Yang J., Nandi S. Growth of mouse mammary gland end buds cultured in a collagen gel matrix. Exp Cell Res. 1982 Oct;141(2):433–443. doi: 10.1016/0014-4827(82)90231-2. [DOI] [PubMed] [Google Scholar]
  40. Rosenthal A., Lindquist P. B., Bringman T. S., Goeddel D. V., Derynck R. Expression in rat fibroblasts of a human transforming growth factor-alpha cDNA results in transformation. Cell. 1986 Jul 18;46(2):301–309. doi: 10.1016/0092-8674(86)90747-6. [DOI] [PubMed] [Google Scholar]
  41. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  42. Salomon D. S., Zwiebel J. A., Bano M., Losonczy I., Fehnel P., Kidwell W. R. Presence of transforming growth factors in human breast cancer cells. Cancer Res. 1984 Sep;44(9):4069–4077. [PubMed] [Google Scholar]
  43. Scott J., Urdea M., Quiroga M., Sanchez-Pescador R., Fong N., Selby M., Rutter W. J., Bell G. I. Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins. Science. 1983 Jul 15;221(4607):236–240. doi: 10.1126/science.6602382. [DOI] [PubMed] [Google Scholar]
  44. Shankar V., Ciardiello F., Kim N., Derynck R., Liscia D. S., Merlo G., Langton B. C., Sheer D., Callahan R., Bassin R. H. Transformation of an established mouse mammary epithelial cell line following transfection with a human transforming growth factor alpha cDNA. Mol Carcinog. 1989;2(1):1–11. doi: 10.1002/mc.2940020102. [DOI] [PubMed] [Google Scholar]
  45. Shyamala G., Ferenczy A. Mammary fat pad may be a potential site for initiation of estrogen action in normal mouse mammary glands. Endocrinology. 1984 Sep;115(3):1078–1081. doi: 10.1210/endo-115-3-1078. [DOI] [PubMed] [Google Scholar]
  46. Singletary S. E., Baker F. L., Spitzer G., Tucker S. L., Tomasovic B., Brock W. A., Ajani J. A., Kelly A. M. Biological effect of epidermal growth factor on the in vitro growth of human tumors. Cancer Res. 1987 Jan 15;47(2):403–406. [PubMed] [Google Scholar]
  47. Taketani Y., Oka T. Possible physiological role of epidermal growth factor in the development of the mouse mammary gland during pregnancy. FEBS Lett. 1983 Feb 21;152(2):256–260. doi: 10.1016/0014-5793(83)80391-3. [DOI] [PubMed] [Google Scholar]
  48. Teixidó J., Gilmore R., Lee D. C., Massagué J. Integral membrane glycoprotein properties of the prohormone pro-transforming growth factor-alpha. 1987 Apr 30-May 6Nature. 326(6116):883–885. doi: 10.1038/326883a0. [DOI] [PubMed] [Google Scholar]
  49. Tonelli Q. J., Sorof S. Epidermal growth factor requirement for development of cultured mammary gland. Nature. 1980 May 22;285(5762):250–252. doi: 10.1038/285250a0. [DOI] [PubMed] [Google Scholar]
  50. Twardzik D. R. Differential expression of transforming growth factor-alpha during prenatal development of the mouse. Cancer Res. 1985 Nov;45(11 Pt 1):5413–5416. [PubMed] [Google Scholar]
  51. Valverius E. M., Bates S. E., Stampfer M. R., Clark R., McCormick F., Salomon D. S., Lippman M. E., Dickson R. B. Transforming growth factor alpha production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells. Mol Endocrinol. 1989 Jan;3(1):203–214. doi: 10.1210/mend-3-1-203. [DOI] [PubMed] [Google Scholar]
  52. Vehaskari V. M., Hering-Smith K. S., Moskowitz D. W., Weiner I. D., Hamm L. L. Effect of epidermal growth factor on sodium transport in the cortical collecting tubule. Am J Physiol. 1989 May;256(5 Pt 2):F803–F809. doi: 10.1152/ajprenal.1989.256.5.F803. [DOI] [PubMed] [Google Scholar]
  53. Williams J. M., Daniel C. W. Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol. 1983 Jun;97(2):274–290. doi: 10.1016/0012-1606(83)90086-6. [DOI] [PubMed] [Google Scholar]
  54. Zajchowski D., Band V., Pauzie N., Tager A., Stampfer M., Sager R. Expression of growth factors and oncogenes in normal and tumor-derived human mammary epithelial cells. Cancer Res. 1988 Dec 15;48(24 Pt 1):7041–7047. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES