Expression of a dominant-negative mutant TGF-β type II receptor in transgenic mice reveals essential roles for TGF-β in regulation of growth and differentiation in the exocrine pancreas

EMBO Journal

Volumn 16, Issue 10, 1997, Pages 2621-2633

  Böttinger, Erwin P ^b   Jakubczak, John L ^a   Roberts, Ian S D ^c   Mumy, Michelle ^a   Hemmati, Philipp ^a   Bagnall, Kerri ^a   Merlino, Glenn ^a   Wakefield, Lalage M ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

In vivo; Receptors; Signal transduction; Transforming growth factor ; Transgenic mice

Indexed keywords

ACTIVIN; MUTANT PROTEIN; RECEPTOR SUBTYPE; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR;

ACINAR CELL; ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL CULTURE; CELL DIFFERENTIATION; CELL INFILTRATION; CONTROLLED STUDY; EPITHELIUM CELL; FIBROSIS; GENE INDUCTION; GROWTH INHIBITION; LIVER CELL; MACROPHAGE; MOUSE; NONHUMAN; ORGAN GROWTH; PANCREAS; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE;

ANIMALS; APOPTOSIS; CELL DIFFERENTIATION; CELL DIVISION; FIBRONECTINS; GENE EXPRESSION; HOMEOSTASIS; IMMUNOHISTOCHEMISTRY; LIVER; METALLOTHIONEIN; MICE; MICE, TRANSGENIC; MUTATION; PANCREAS; PANCREATIC NEOPLASMS; PHENOTYPE; PROLIFERATING CELL NUCLEAR ANTIGEN; PROMOTER REGIONS (GENETICS); RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA;

ANIMALIA; MUS MUSCULUS;

EID: 0342460497     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1093/emboj/16.10.2621     Document Type: Article

References (55)

1. Baldwin, R.L., Friess, H., Yokohama, M., Lopez, M.E., Kobrin, M.S., Büchler, M.W. and Korc, M. (1996) Attenuated ALK5 receptor expression in human pancreatic cancer: correlation with resistance to growth inhibition. Int. J. Cancer, 67, 283-288.
2. Bascom, C.C., Wolfshohl, J.R., Coffey, R.J., Jr, Madisen, L., Webb, N.R., Purchio, A.R., Derynck, R. and Moses, H.L. (1989) 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., 9, 5508-5515.
3. Bockman, D.E. (1981) Cells of origin of pancreatic cancer: experimental animal tumors related to human pancreas. Cancer, 47, 1528-1534.
4. Bockman, D.E. and Merlino, G. (1992) Cytological changes in the pancreas of transgenic mice overexpressing transforming growth factor alpha. Gastroentemlogy, 103, 1883-1892.
5. Bonham, M.J. and Danielpour, D. (1996) Improved purification and yields by RNeasy. BioTechniques, 21, 57-60.
6. Brand, T., MacLellan, W.R. and Schneider, M.D, (1993) A dominant-negative receptor for type beta transforming growth factors created by deletion of the kinase domain. J. Biol. Chem., 268, 11500-11503.
7. Böttinger, E.P. et al. (1996) The recombinant proregion of transforming growth factor β1 (latency-associated peptide) inhibits active transforming growth factor β1 in transgenic mice. Proc. Natl Acad. Sci. USA, 93, 5877-5882.
8. Chen, R.H., Ebner, R. and Derynck, R. (1993) Inactivation of the type II receptor reveals two receptor pathways for the diverse TGF-beta activities. Science, 260, 1335-1338.
9. Cui, W., Fowlis, D.J., Cousins, F.M., Duffie, E., Bryson, S., Balmain, A. and Akhurst, R.J. (1995) Concerted action of TGF-beta 1 and its type II receptor in control of epidermal homeostasis in transgenic mice. Genes Dev., 9, 945-955.
10. De Lisle, R.C. and Logsdon, C.D. (1990) Pancreatic acinar cells in culture: expression of acinar and ductal antigens in a growth-related manner. Eur. J. Cell Biol., 51, 64-75.
11. Eustis, S.L., Boorman, G.A. and Hayashi, Y. (1990) Exocrine pancreas. In Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery, C.A. and MacKenzie, W.F. (eds), Pathology of the Fischer Rat. Academic Press, Inc., San Diego, pp. 95-108.
12. Evan, G.I., Wyllie, A.H., Gilbert, C.S., Littlewood, T.D., Land, H., Brooks, M., Waters, C.M., Penn, L.Z. and Hancock, D.C. (1992) Induction of apoptosis in fibroblasts by c-myc protein. Cell, 69, 119-128.
13. Flaks, B. (1984) Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence. Environ. Health Perspect., 56, 187-203.
14. Flanders, K.C., Thompson, N.L., Cissel, D.S., Van Obberghen-Schilling, E., Baker, C.C., Kass, M.E., Ellingsworth, L.R., Roberts, A.B. and Sporn, M.B. (1989) Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes. J. Cell Biol., 108, 653-660.
15. Flanders, K.C., Cissel, D.S., Mullen, L.T., Danielpour, D., Sporn, M.B. and Roberts, A.B. (1990) Antibodies to transforming growth factor-beta 2 peptides: specific detection of TGF-beta 2 in immunoassays. Growth Factors, 3, 45-52.
16. Flanders, K.C., Ludecke, G., Engels, S., Cissel, D.S., Roberts, A.B., Kondaiah, P. Lafyatis, R., Sporn, M.B. and Unsicker, K. (1991) Localization and actions of transforming growth factor-betas in the embryonic nervous system. Development, 113, 183-191.
17. Friess, H., Yamanaka, Y., Buchler, M., Ebert, M., Beger, H.G., Gold, L.I. and Korc, M. (1993) Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology, 105, 1846-1856.
18. Frolik, C.A., Wakefield, L.M., Smith, D.M. and Sporn, M.B. (1984) Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. J. Biol. Chem., 259, 10995-11000.
19. Geiser, A.G., Burmester, J.K., Webbink, R., Roberts, A.B. and Sporn, M.B. (1992) Inhibition of growth by transforming growth factor-beta following fusion of two nonresponsive human carcinoma cell lines. Implication of the type II receptor in growth inhibitory responses. J. Biol Chem., 267, 2588-2593.
20. Githens, S. (1993) Differentiation and development of the pancreas in animals. In The Pancreas: Biology, Pathobiology and Disease. Go, V.L.W., DiMagno, E.P., Gardner, J.D., Lebenthal, E., Reber, H.A. and Scheele, G.A. (eds). Raven Press, New York, pp. 21-55.
21. Gold, L.I. and Korc, M. (1994) Expression of transforming growth factor-β1, 2 and 3 mRNA and protein in human cancers. Digest. Surg., 11, 150-156.
22. Gold, L.I., Saxena, B., Mittal, K.R., Marmor, M., Goswami, S., Nactigal, L., Korc, M. and Demopoulos, R.I. (1994) Increased expression of transforming growth factor beta isoforms and basic fibroblast growth factor in complex hyperplasia and adenocarcinoma of the endometrium: evidence for paracrine and autocrine action. Cancer Res., 54, 2347-2358.
23. Gorsch, S.M., Memoli, V.A., Stukel, T.A., Gold, L.I. and Arrick, B.A. (1992) Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. Cancer Res., 52, 6949-6952.
24. Hahn, S.A. et al. (1996) DPC4, a candidate tumor supressor gene at chromosome 18q21.1. Science, 271, 350-353.
25. Howes, K.A., Ransom, N., Papermaster, D.S., Lasudry, J.G.H., Albert, D.M. and Windle, J.J. (1994) Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53. Genes Dev., 8, 1300-1310.
26. Hsing, A.Y., Kadomatsu, K., Bonham, M.J. and Danielpour, D. (1996) Regulation of apoptosis induced by transforming growth factor-β1 in nontumorigenic and tumorigenic rat prostatic epithelial cell lines. Cancer Res., 56, 5146-5149.
27. Jacks, T., Fazeli, A., Schmitt, E.M., Bronson, R.T. Goodell, M.A. and Weinberg, R.A. (1992) Effects of an Rb mutation in the mouse. Nature, 359, 295-300.
28. Jhappan, C., Stahle, C., Harkins, R.N., Fausto, N., Smith, G.H. and Merlino, G.T. (1990) TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell, 61, 1137-1146.
29. Kim, S.J., Angel, P., Lafyatis, R., Hattori, K., Kim, K.Y., Sporn, M.B., Karin, M. and Roberts, A.B. (1990) Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex. Mol. Cell. Biol., 10, 1492-1497.
30. Kulkarni, A.B. et al. (1993) Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl Acad. Sci. USA, 90, 770-774.
31. Lagna, G., Hata, A., Hemmati-Brivanlou, A. and Massague, J. (1996) Partnership between DPC4 and SMAD proteins in TGF-β signalling pathways. Nature, 383, 832-836.
32. Lee, M.S. et al. (1995) Accumulation of extracellular matrix and developmental dysregulation in the pancreas by transgenic production of transforming growth factor-beta 1. Am. J. Pathol., 147, 42-52.
33. Logsdon, C.D. (1995) Pancreatic duct cell cultures: there is more to ducts than salty water. Gastroenterology, 109, 1005-1009.
34. Logsdon, C.D. and Williams, J.A. (1983) Pancreatic acini in short-term culture: regulation by EGF, carbachol, insulin and corticosterone. Am. J. Physiol., 244, G675-G682.
35. Logsdon, C.D., Keyes, L. and Beauchamp, R.D. (1992) Transforming growth factor-beta (TGF-beta 1) inhibits pancreatic acinar cell growth. Am. J. Physiol., 262, G364-G368.
36. Markowitz, S.D. and Roberts, A.B. (1996) Tumor suppressor activity of the TGF-β pathway in human cancers. Cytokine Growth Factor Rev., 1, 93-102.
37. Millan, F.A., Denhez, F., Kondaiah, P. and Akhurst, R.J. (1991) Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo. Development, 111, 131-143.
38. Naik, P., Karrim, J. and Hanahan, D. (1996) The rise and fall of apoptosis during multistage tumorigenesis: down-modulation contributes to tumor progression from angiogenic progenitors. Genes Dev., 10, 2105-2116.
39. Nathan, C. and Sporn, M. (1991) Cytokines in context. J. Cell Biol., 113, 981-986.
40. Oberhammer, F.A., Pavelka, M., Sharma, S., Tiefenbacher, R., Purchio, A.F., Bursch, W. and Schulte-Hermann, R. (1992) Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor beta 1. Proc. Natl Acad. Sci. USA, 89, 5408-5412.
41. Ornitz, D.M., Hammer, R.E., Messing, A., Palmiter, R.D. and Brinster, R.L. (1987) Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science, 238, 188-193.
42. Palmiter, R.D., Sandgren, E.P. Koeller, D.M. and Brinster, R.L. (1993) Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice. Mol. Cell. Biol., 13, 5266-5275.
43. Parsa, I., Longnecker, D.S., Scarpelli, D.G., Pour, P., Reddy, J.K. and Lefkowitz, M. (1985) Ductal metaplasia of human exocrine pancreas and its association with carcinoma. Cancer Res., 45, 1285-1290.
44. Pierce, D.F., Jr, Gorska, A.E., Chytil, A., Meise, K.S., Page, D.L., Coffey, R.J., Jr and Moses, H.L. (1995) Mammary tumor suppression by transforming growth factor beta 1 transgene expression. Proc. Natl Acad. Sci. USA, 92, 4254-4258.
45. Pierce, G.F., Mustoe, T.A., Lingelbach, J., Masakowski, V.R., Griffin, G.L., Senior, R.M. and Deuel, T.F. (1989) Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. J. Cell Biol., 109, 429-440.
46. Roberts, A.B. et al. (1986) Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Natl Acad. Sci. USA, 83, 4167-4171.
47. Roberts, A.B. and Sporn, M.B. (1990) The transforming growth factors-β. In Sporn, M.B. and Roberts, A.B. (eds), Handbook of Experimental Pharmacology. Peptide Growth Factors and Their Receptors. Springer-Verlag, Berlin, pp. 419-472.
48. Sandgren, E.P., Luetteke, N.C., Palmiter, R.D., Brinster, R.L. and Lee, D.C. (1990) Overexpression of TGF-alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia and carcinoma of the breast. Cell, 61, 1121-1135.
49. Sandgren, E.P., Quaife, C.J., Paulovich, A.G., Palmiter, R.D. and Brinster, R.L. (1991) Pancreatic tumor pathogenesis reflects the causative genetic lesion. Proc. Natl Acad. Sci. USA, 88, 93-97.
50. Scarpelli, D.G., Rao, M.S. and Reddy, J.K. (1984) Studies of pancreatic carcinogenesis in different animal models. Environ. Health Perspect., 56, 219-227.
51. Seifert, G. (1984) Lipomatous atrophy and other forms. In Kloppel, G. and Heitz, P.U. (eds), Pancreatic Pathology. Churchill Livingstone, Edinburgh, pp. 27-31.
52. White, E. (1996) Life, death and the pursuit of apoptosis. Genes Dev., 10, 1-15.
53. Wrana, J.L., Attisano, L., C:arcamo, J., Zentella, A., Doody, J., Laiho, M., Wang, X.F. and Massague, J. (1992) TGF beta signals through a heteromeric protein kinase receptor complex. Cell, 71, 1003-1014.
54. Wrana, J.L., Attisano, L., Wieser, R., Ventura, F. and Massague, J. (1994) Mechanism of activation of the TGF-beta receptor. Nature, 370, 341-347.
55. Zhang, Y., Feng, X.H., Wu, R.Y. and Derynck, R. (1996) Receptor-associated Mad homologues synergize as effectors of the TGF-β response. Nature, 383, 168-172.