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. 1990 Nov;1(12):875–882. doi: 10.1091/mbc.1.12.875

TGF-beta: problems and prospects.

M B Sporn 1, A B Roberts 1
PMCID: PMC362858  PMID: 2100192

Abstract

TGF-beta research is proceeding at an exponential pace. Studies in this area have become increasingly relevant to many areas of cell regulation, continually providing new surprises and findings. One may confidently predict that TGF-beta will be one of the key molecules in future attempts to establish an integrated view of the processes whereby cells coordinate their own and mutual functions. We have seen only the beginning, and this minireview is only a glimpse.

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Selected References

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

  1. Assoian R. K., Komoriya A., Meyers C. A., Miller D. M., Sporn M. B. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed] [Google Scholar]
  2. Baird A., Durkin T. Inhibition of endothelial cell proliferation by type beta-transforming growth factor: interactions with acidic and basic fibroblast growth factors. Biochem Biophys Res Commun. 1986 Jul 16;138(1):476–482. doi: 10.1016/0006-291x(86)90305-0. [DOI] [PubMed] [Google Scholar]
  3. Bascom C. C., Wolfshohl J. R., Coffey R. J., Jr, Madisen L., Webb N. R., Purchio A. R., Derynck R., Moses H. L. Complex regulation of transforming growth factor beta 1, beta 2, and beta 3 mRNA expression in mouse fibroblasts and keratinocytes by transforming growth factors beta 1 and beta 2. Mol Cell Biol. 1989 Dec;9(12):5508–5515. doi: 10.1128/mcb.9.12.5508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beck L. S., Chen T. L., Hirabayashi S. E., Deguzman L., Lee W. P., McFatridge L. L., Xu Y., Bates R. L., Ammann A. J. Accelerated healing of ulcer wounds in the rabbit ear by recombinant human transforming growth factor-beta 1. Growth Factors. 1990;2(4):273–282. doi: 10.3109/08977199009167022. [DOI] [PubMed] [Google Scholar]
  5. Braun L., Dürst M., Mikumo R., Gruppuso P. Differential response of nontumorigenic and tumorigenic human papillomavirus type 16-positive epithelial cells to transforming growth factor beta 1. Cancer Res. 1990 Nov 15;50(22):7324–7332. [PubMed] [Google Scholar]
  6. Brown P. D., Wakefield L. M., Levinson A. D., Sporn M. B. Physicochemical activation of recombinant latent transforming growth factor-beta's 1, 2, and 3. Growth Factors. 1990;3(1):35–43. doi: 10.3109/08977199009037500. [DOI] [PubMed] [Google Scholar]
  7. Buchkovich K., Duffy L. A., Harlow E. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell. 1989 Sep 22;58(6):1097–1105. doi: 10.1016/0092-8674(89)90508-4. [DOI] [PubMed] [Google Scholar]
  8. Chambard J. C., Pouysségur J. TGF-beta inhibits growth factor-induced DNA synthesis in hamster fibroblasts without affecting the early mitogenic events. J Cell Physiol. 1988 Apr;135(1):101–107. doi: 10.1002/jcp.1041350114. [DOI] [PubMed] [Google Scholar]
  9. Cheifetz S., Weatherbee J. A., Tsang M. L., Anderson J. K., Mole J. E., Lucas R., Massagué J. The transforming growth factor-beta system, a complex pattern of cross-reactive ligands and receptors. Cell. 1987 Feb 13;48(3):409–415. doi: 10.1016/0092-8674(87)90192-9. [DOI] [PubMed] [Google Scholar]
  10. Chen P. L., Scully P., Shew J. Y., Wang J. Y., Lee W. H. Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell. 1989 Sep 22;58(6):1193–1198. doi: 10.1016/0092-8674(89)90517-5. [DOI] [PubMed] [Google Scholar]
  11. Coffey R. J., Jr, Bascom C. C., Sipes N. J., Graves-Deal R., Weissman B. E., Moses H. L. Selective inhibition of growth-related gene expression in murine keratinocytes by transforming growth factor beta. Mol Cell Biol. 1988 Aug;8(8):3088–3093. doi: 10.1128/mcb.8.8.3088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Coffman R. L., Lebman D. A., Shrader B. Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. J Exp Med. 1989 Sep 1;170(3):1039–1044. doi: 10.1084/jem.170.3.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Colletta A. A., Wakefield L. M., Howell F. V., van Roozendaal K. E., Danielpour D., Ebbs S. R., Sporn M. B., Baum M. Anti-oestrogens induce the secretion of active transforming growth factor beta from human fetal fibroblasts. Br J Cancer. 1990 Sep;62(3):405–409. doi: 10.1038/bjc.1990.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DeCaprio J. A., Ludlow J. W., Lynch D., Furukawa Y., Griffin J., Piwnica-Worms H., Huang C. M., Livingston D. M. The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell. 1989 Sep 22;58(6):1085–1095. doi: 10.1016/0092-8674(89)90507-2. [DOI] [PubMed] [Google Scholar]
  15. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  16. Derynck R., Lindquist P. B., Lee A., Wen D., Tamm J., Graycar J. L., Rhee L., Mason A. J., Miller D. A., Coffey R. J. A new type of transforming growth factor-beta, TGF-beta 3. EMBO J. 1988 Dec 1;7(12):3737–3743. doi: 10.1002/j.1460-2075.1988.tb03257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Frolik C. A., Dart L. L., Meyers C. A., Smith D. M., Sporn M. B. Purification and initial characterization of a type beta transforming growth factor from human placenta. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3676–3680. doi: 10.1073/pnas.80.12.3676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gentry L. E., Nash B. W. The pro domain of pre-pro-transforming growth factor beta 1 when independently expressed is a functional binding protein for the mature growth factor. Biochemistry. 1990 Jul 24;29(29):6851–6857. doi: 10.1021/bi00481a014. [DOI] [PubMed] [Google Scholar]
  20. Gentry L. E., Webb N. R., Lim G. J., Brunner A. M., Ranchalis J. E., Twardzik D. R., Lioubin M. N., Marquardt H., Purchio A. F. Type 1 transforming growth factor beta: amplified expression and secretion of mature and precursor polypeptides in Chinese hamster ovary cells. Mol Cell Biol. 1987 Oct;7(10):3418–3427. doi: 10.1128/mcb.7.10.3418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Glick A. B., Flanders K. C., Danielpour D., Yuspa S. H., Sporn M. B. Retinoic acid induces transforming growth factor-beta 2 in cultured keratinocytes and mouse epidermis. Cell Regul. 1989 Nov;1(1):87–97. doi: 10.1091/mbc.1.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Green S., Chambon P. A superfamily of potentially oncogenic hormone receptors. Nature. 1986 Dec 18;324(6098):615–617. doi: 10.1038/324615a0. [DOI] [PubMed] [Google Scholar]
  23. Hebda P. A. Stimulatory effects of transforming growth factor-beta and epidermal growth factor on epidermal cell outgrowth from porcine skin explant cultures. J Invest Dermatol. 1988 Nov;91(5):440–445. doi: 10.1111/1523-1747.ep12476480. [DOI] [PubMed] [Google Scholar]
  24. Jakowlew S. B., Dillard P. J., Sporn M. B., Roberts A. B. Complementary deoxyribonucleic acid cloning of a messenger ribonucleic acid encoding transforming growth factor beta 4 from chicken embryo chondrocytes. Mol Endocrinol. 1988 Dec;2(12):1186–1195. doi: 10.1210/mend-2-12-1186. [DOI] [PubMed] [Google Scholar]
  25. Kanzaki T., Olofsson A., Morén A., Wernstedt C., Hellman U., Miyazono K., Claesson-Welsh L., Heldin C. H. TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences. Cell. 1990 Jun 15;61(6):1051–1061. doi: 10.1016/0092-8674(90)90069-q. [DOI] [PubMed] [Google Scholar]
  26. Kim S. J., Angel P., Lafyatis R., Hattori K., Kim K. Y., Sporn M. B., Karin M., Roberts A. B. Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex. Mol Cell Biol. 1990 Apr;10(4):1492–1497. doi: 10.1128/mcb.10.4.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kim S. J., Jeang K. T., Glick A. B., Sporn M. B., Roberts A. B. Promoter sequences of the human transforming growth factor-beta 1 gene responsive to transforming growth factor-beta 1 autoinduction. J Biol Chem. 1989 Apr 25;264(12):7041–7045. [PubMed] [Google Scholar]
  28. Kimchi A., Wang X. F., Weinberg R. A., Cheifetz S., Massagué J. Absence of TGF-beta receptors and growth inhibitory responses in retinoblastoma cells. Science. 1988 Apr 8;240(4849):196–199. doi: 10.1126/science.2895499. [DOI] [PubMed] [Google Scholar]
  29. Kondaiah P., Sands M. J., Smith J. M., Fields A., Roberts A. B., Sporn M. B., Melton D. A. Identification of a novel transforming growth factor-beta (TGF-beta 5) mRNA in Xenopus laevis. J Biol Chem. 1990 Jan 15;265(2):1089–1093. [PubMed] [Google Scholar]
  30. Lafyatis R., Lechleider R., Kim S. J., Jakowlew S., Roberts A. B., Sporn M. B. Structural and functional characterization of the transforming growth factor beta 3 promoter. A cAMP-responsive element regulates basal and induced transcription. J Biol Chem. 1990 Nov 5;265(31):19128–19136. [PubMed] [Google Scholar]
  31. Laiho M., DeCaprio J. A., Ludlow J. W., Livingston D. M., Massagué J. Growth inhibition by TGF-beta linked to suppression of retinoblastoma protein phosphorylation. Cell. 1990 Jul 13;62(1):175–185. doi: 10.1016/0092-8674(90)90251-9. [DOI] [PubMed] [Google Scholar]
  32. Lefer A. M., Tsao P., Aoki N., Palladino M. A., Jr Mediation of cardioprotection by transforming growth factor-beta. Science. 1990 Jul 6;249(4964):61–64. doi: 10.1126/science.2164258. [DOI] [PubMed] [Google Scholar]
  33. Lyons R. M., Moses H. L. Transforming growth factors and the regulation of cell proliferation. Eur J Biochem. 1990 Feb 14;187(3):467–473. doi: 10.1111/j.1432-1033.1990.tb15327.x. [DOI] [PubMed] [Google Scholar]
  34. Madri J. A., Pratt B. M., Tucker A. M. Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix. J Cell Biol. 1988 Apr;106(4):1375–1384. doi: 10.1083/jcb.106.4.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Massagué J. The transforming growth factor-beta family. Annu Rev Cell Biol. 1990;6:597–641. doi: 10.1146/annurev.cb.06.110190.003121. [DOI] [PubMed] [Google Scholar]
  36. Mihara K., Cao X. R., Yen A., Chandler S., Driscoll B., Murphree A. L., T'Ang A., Fung Y. K. Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product. Science. 1989 Dec 8;246(4935):1300–1303. doi: 10.1126/science.2588006. [DOI] [PubMed] [Google Scholar]
  37. Miyazono K., Hellman U., Wernstedt C., Heldin C. H. Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization. J Biol Chem. 1988 May 5;263(13):6407–6415. [PubMed] [Google Scholar]
  38. O'Malley B. The steroid receptor superfamily: more excitement predicted for the future. Mol Endocrinol. 1990 Mar;4(3):363–369. doi: 10.1210/mend-4-3-363. [DOI] [PubMed] [Google Scholar]
  39. Pietenpol J. A., Holt J. T., Stein R. W., Moses H. L. Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation. Proc Natl Acad Sci U S A. 1990 May;87(10):3758–3762. doi: 10.1073/pnas.87.10.3758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pietenpol J. A., Stein R. W., Moran E., Yaciuk P., Schlegel R., Lyons R. M., Pittelkow M. R., Münger K., Howley P. M., Moses H. L. TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell. 1990 Jun 1;61(5):777–785. doi: 10.1016/0092-8674(90)90188-k. [DOI] [PubMed] [Google Scholar]
  41. Roberts A. B., Anzano M. A., Meyers C. A., Wideman J., Blacher R., Pan Y. C., Stein S., Lehrman S. R., Smith J. M., Lamb L. C. Purification and properties of a type beta transforming growth factor from bovine kidney. Biochemistry. 1983 Dec 6;22(25):5692–5698. doi: 10.1021/bi00294a002. [DOI] [PubMed] [Google Scholar]
  42. Roberts A. B., Anzano M. A., Wakefield L. M., Roche N. S., Stern D. F., Sporn M. B. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985 Jan;82(1):119–123. doi: 10.1073/pnas.82.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rosen D. M., Stempien S. A., Thompson A. Y., Seyedin S. M. Transforming growth factor-beta modulates the expression of osteoblast and chondroblast phenotypes in vitro. J Cell Physiol. 1988 Mar;134(3):337–346. doi: 10.1002/jcp.1041340304. [DOI] [PubMed] [Google Scholar]
  45. Ruoslahti E., Pierschbacher M. D. Arg-Gly-Asp: a versatile cell recognition signal. Cell. 1986 Feb 28;44(4):517–518. doi: 10.1016/0092-8674(86)90259-x. [DOI] [PubMed] [Google Scholar]
  46. Sager R. Tumor suppressor genes: the puzzle and the promise. Science. 1989 Dec 15;246(4936):1406–1412. doi: 10.1126/science.2574499. [DOI] [PubMed] [Google Scholar]
  47. Seyedin S. M., Segarini P. R., Rosen D. M., Thompson A. Y., Bentz H., Graycar J. Cartilage-inducing factor-B is a unique protein structurally and functionally related to transforming growth factor-beta. J Biol Chem. 1987 Feb 15;262(5):1946–1949. [PubMed] [Google Scholar]
  48. Seyedin S. M., Thomas T. C., Thompson A. Y., Rosen D. M., Piez K. A. Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2267–2271. doi: 10.1073/pnas.82.8.2267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Seyedin S. M., Thompson A. Y., Bentz H., Rosen D. M., McPherson J. M., Conti A., Siegel N. R., Galluppi G. R., Piez K. A. Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta. J Biol Chem. 1986 May 5;261(13):5693–5695. [PubMed] [Google Scholar]
  50. Shipley G. D., Pittelkow M. R., Wille J. J., Jr, Scott R. E., Moses H. L. Reversible inhibition of normal human prokeratinocyte proliferation by type beta transforming growth factor-growth inhibitor in serum-free medium. Cancer Res. 1986 Apr;46(4 Pt 2):2068–2071. [PubMed] [Google Scholar]
  51. Smeland E. B., Blomhoff H. K., Holte H., Ruud E., Beiske K., Funderud S., Godal T., Ohlsson R. Transforming growth factor type beta (TGF beta) inhibits G1 to S transition, but not activation of human B lymphocytes. Exp Cell Res. 1987 Jul;171(1):213–222. doi: 10.1016/0014-4827(87)90264-3. [DOI] [PubMed] [Google Scholar]
  52. Sporn M. B. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res. 1976 Jul;36(7 Pt 2):2699–2702. [PubMed] [Google Scholar]
  53. Sporn M. B., Roberts A. B. Peptide growth factors are multifunctional. Nature. 1988 Mar 17;332(6161):217–219. doi: 10.1038/332217a0. [DOI] [PubMed] [Google Scholar]
  54. Sporn M. B., Roberts A. B., Wakefield L. M., de Crombrugghe B. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol. 1987 Sep;105(3):1039–1045. doi: 10.1083/jcb.105.3.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Thompson N. L., Bazoberry F., Speir E. H., Casscells W., Ferrans V. J., Flanders K. C., Kondaiah P., Geiser A. G., Sporn M. B. Transforming growth factor beta-1 in acute myocardial infarction in rats. Growth Factors. 1988;1(1):91–99. doi: 10.3109/08977198809000251. [DOI] [PubMed] [Google Scholar]
  56. Tsunawaki S., Sporn M., Ding A., Nathan C. Deactivation of macrophages by transforming growth factor-beta. Nature. 1988 Jul 21;334(6179):260–262. doi: 10.1038/334260a0. [DOI] [PubMed] [Google Scholar]
  57. Wahl S. M., McCartney-Francis N., Allen J. B., Dougherty E. B., Dougherty S. F. Macrophage production of TGF-beta and regulation by TGF-beta. Ann N Y Acad Sci. 1990;593:188–196. doi: 10.1111/j.1749-6632.1990.tb16111.x. [DOI] [PubMed] [Google Scholar]
  58. Wakefield L. M., Smith D. M., Broz S., Jackson M., Levinson A. D., Sporn M. B. Recombinant TGF-beta 1 is synthesized as a two-component latent complex that shares some structural features with the native platelet latent TGF-beta 1 complex. Growth Factors. 1989;1(3):203–218. doi: 10.3109/08977198908997997. [DOI] [PubMed] [Google Scholar]
  59. Wakefield L. M., Smith D. M., Flanders K. C., Sporn M. B. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem. 1988 Jun 5;263(16):7646–7654. [PubMed] [Google Scholar]
  60. Wakefield L. M., Sporn M. B. Suppression of carcinogenesis: a role for TGF-beta and related molecules in prevention of cancer. Immunol Ser. 1990;51:217–243. [PubMed] [Google Scholar]
  61. Webb N. R., Madisen L., Rose T. M., Purchio A. F. Structural and sequence analysis of TGF-beta 2 cDNA clones predicts two different precursor proteins produced by alternative mRNA splicing. DNA. 1988 Sep;7(7):493–497. doi: 10.1089/dna.1.1988.7.493. [DOI] [PubMed] [Google Scholar]
  62. Woodworth C. D., Notario V., DiPaolo J. A. Transforming growth factors beta 1 and 2 transcriptionally regulate human papillomavirus (HPV) type 16 early gene expression in HPV-immortalized human genital epithelial cells. J Virol. 1990 Oct;64(10):4767–4775. doi: 10.1128/jvi.64.10.4767-4775.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wrann M., Bodmer S., de Martin R., Siepl C., Hofer-Warbinek R., Frei K., Hofer E., Fontana A. T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. EMBO J. 1987 Jun;6(6):1633–1636. doi: 10.1002/j.1460-2075.1987.tb02411.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Yamaguchi Y., Mann D. M., Ruoslahti E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature. 1990 Jul 19;346(6281):281–284. doi: 10.1038/346281a0. [DOI] [PubMed] [Google Scholar]
  65. ten Dijke P., Hansen P., Iwata K. K., Pieler C., Foulkes J. G. Identification of another member of the transforming growth factor type beta gene family. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4715–4719. doi: 10.1073/pnas.85.13.4715. [DOI] [PMC free article] [PubMed] [Google Scholar]

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