The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor β in fetal rat hepatocytes

Molecular Cancer Research

Volumn 1, Issue 1, 2002, Pages 68-78

  Valdés, Francisco ^a   Álvarez, Alberto M ^a   Locascio, Annamaria ^b   Vega, Sonia ^b   Herrera, Blanca ^a   Fernández, Margarita ^a   Benito, Manuel ^a   Nieto, M Angela ^b   Fabregat, Isabel ^a  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b INSTITUTO CAJAL   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CYTOKERATIN 18; DNA; HEPATOCYTE NUCLEAR FACTOR 4; NUCLEAR FACTOR I; PROTEIN BCL XL; PROTEIN KINASE B; RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR SNAIL; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UVOMORULIN; VIMENTIN;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL CYCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CONTROLLED STUDY; DNA CONTENT; EPITHELIUM CELL; FETUS; LIVER CELL; LIVER CELL CARCINOMA; MESENCHYME; NONHUMAN; PRIORITY JOURNAL; RAT; SERUM; STEM CELL;

ANIMALS; ANTIGENS, DIFFERENTIATION; APOPTOSIS; BCL-X PROTEIN; CELL MOVEMENT; CELLS, CULTURED; CULTURE MEDIA, CONDITIONED; CULTURE MEDIA, SERUM-FREE; DNA-BINDING PROTEINS; EPITHELIAL CELLS; FEMALE; GENE EXPRESSION REGULATION; HEPATOCYTES; HUMANS; MESODERM; PREGNANCY; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-BCL-2; RATS; RATS, WISTAR; RECOMBINANT PROTEINS; TRANSCRIPTION FACTORS; TRANSFORMING GROWTH FACTOR BETA; VIMENTIN;

ANIMALIA; BOVINAE; GASTROPODA;

EID: 0344406127     PISSN: 15417786     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (48)

1. Grasl-Kraupp, B., Ruttkay-Nedecky, B., Mullauer, L., Taper, H., Huber, W., Bursch, W., and Schulte-Hermann, R. Inherent increase of apoptosis in liver tumors: implications for carcinogenesis and tumor repression. Hepatology, 25: 906-912, 1997.
2. Pitot, H. C. Hepatocyte death in hepatocarcinogenesis. Hepatology, 28: 1-5, 1998.
3. Rust, C. and Gores, G. J. Apoptosis and liver disease. Am. J. Med., 108: 567-574, 2000.
4. Derynck, R., Akhurst, R. J., and Balmain, A. TGF-β signaling suppression and cancer progression. Nat. Genet., 29: 117-129, 2001.
5. Wollenberg, G. K., Semple, E., Quinn, B. A., and Hayes, M. A. Inhibition of proliferation of normal, preneoplastic and neoplastic rat hepatocytes by transforming growth factor-β. Cancer Res., 47: 6595-6599, 1987.
6. Serra, R., Carbonetto, S., Lord, M., and Isom, H. C. Transforming growth factor β1 suppresses transformation in hepatocytes by regulating α1β1 integrin expression. Cell Growth & Differ., 5: 509-517, 1984.
7. Oberhammer, F. A., Pavelka, M., Sharma, S., Tiefenbacher, R., Purchio, A. F., Bursch, W., and Schulte-Hermann, R. Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor β 1. Proc. Natl. Acad. Sci. USA, 89: 5408-5412, 1992.
8. Thorgeirsson, S. S., Teramoto, T., and Factor, V. Regulation of apoptosis in hepatocellular carcinoma. Semin. Liver Dis., 18: 115-122, 1998.
9. Rossmanith, W. and Schulte-Hermann, R. Biology of transforming growth factor β in hepatocarcinogenesis. Microsc. Res. Tech., 52: 430-436, 2001.
10. Tsai, J. F., Jeng, J. E., Chuang, L. Y., Yang, M. L., Ho, M. S., Chang, W. Y., Hsich, M. Y., Lin, Z. Y., and Tsai, J. H. Elevated urinary transforming growth factor-β1 level as a tumour marker and predictor of poor survival in cirrhotic hepatocellular carcinoma. Br. J. Cancer, 76: 244-250, 1997.
11. Factor, V. M., Kao, C. Y., Santoni-Rugiu, E., Woitach, J. T., Jensen, M. R., and Thorgeirsson, S. S. Constitutive expression of mature transforming growth factor β1 in liver accelerates hepatocarcinogenesis in transgenic mice. Cancer Res., 57: 2089-2095, 1997.
12. Zhang, X., Wang, T., Batist G., and Tsao, M. S. Transforming growth factor β1 promotes spontaneous transformation of cultured rat liver epithelial cells. Cancer Res., 54: 6122-6128, 1994.
13. De Juan, C., Benito, M., Alvarez, A. M., and Fabregat, I. Differential proliferative response of cultured fetal and regenerating hepatocytes to growth factors and hormones. Exp. Cell Res., 202: 495-500, 1992.
14. Sánchez, A., Álvarez, A. M., Benito, M., and Fabregat, I. Apoptosis induced by transforming growth factor-β in fetal hepatocyte primary cultures. J. Biol. Chem., 271: 7416-7422, 1996.
15. Herrera, B., Álvarez, A. M., Sánchez, A., Fernández, M., Roncero, C., Benito, M., and Fabregat, I. Mitochondrial permeability transition induced by TGF-β in fetal hepatocytes in primary culture. Role of reactive oxygen species (ROS) upstream the mitochondria. FASEB J., 15: 741-751, 2001.
16. Sánchez, A., Álvarez, A. M., López Pedrosa, J. M., Roncero, C., Benito, M., and Fabregat, I. Apoptotic response to TGF-β in fetal hepatocytes depends upon their state of differentiation. Exp. Cell Res., 252: 281-291, 1999.
17. Pagan, R., Sánchez, A., Martin, M., Llobera, M., Fabregat, I., and Vilaró, S. Effects of growth and differentiation factors on the epithelial-mesenchymal transition in cultured neonatal rat hepatocytes. J. Hepatol., 31: 895-904, 1999.
18. Hay, E. D. An overview of epithelio-mesenchymal transformation. Acta Anat., 154: 8-20, 1995.
19. Nieto, M. A., Sargent, M., Wilkinson, D. G., and Cooke, J. Control of cell behaviour during vertebrate development by Slug, a Zinc finger gene. Science, 264: 835-839, 1994.
20. Cano, A., Pérez-Moreno, M. A., Rodrigo, I., Locascio, A., Blanco, M. J., del Barrio, M. G., Portillo, F., and Nieto, M. A. The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol., 2: 76-83, 2000.
21. Carver, E. A., Jiang, R., Lan, Y., Oram, K. F., and Gridley, T. The mouse Snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol. Cell. Biol., 21: 8184-8188, 2001.
22. Battle, E., Sancho, E., Franci, C., Domínguez, D., Monfar, M., Baulida, J., and García de Herreros, A. The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol., 2: 84-89, 2000.
23. Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., Marcel, M., Huylebroeck, D., and van Roy, F. The two-handed E box binding zinc finger protein SIPI down-regulates E-cadherin and induces invasion. Mol. Cell, 7: 1267-1278, 2001.
24. Pérez-Moreno, M., Locascio, A., Rodrigo, I., Dhont, G., Portillo, F., Nieto, M. A., and Cano, A. A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transition. J. Biol. Chem., 276: 27424-27431, 2001.
25. Cheng, C. W., Wu, P. E., Yu, J. C., Huang, C. S., Yue, C. T., Wu, C. W., and Shen, C. Y. Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene, 20: 3814-3823, 2001.
26. Blanco, M. J., Moreno-Bueno, G., Sarrio, D., Locascio, A., Cano, A., Palacios, J., and Nieto, M. A. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene, 21: 3241-3246, 2002.
27. Leffert, H. L., Koch, K. S., Moran, T., and Williams, M. Liver cells. Methods Enzymol., 58: 536-544, 1979.
28. Dunsford, H. A., Karnasuta, C., Hunt, J. M., and Sell, S. Different lineages of chemically induced hepatocellular carcinoma in rats defined by monoclonal antibodies. Cancer Res., 49: 4894-4900, 1989.
29. Fabregat, I., Herrera, B., Fernández, M., Álvarez, A. M., Sánchez, A., Roncero, C., Ventura, J. J., and Benito, M. Epidermal growth factor impairs the cytochrome c/caspase 3 apoptotic pathway induced by TGF-β in rat fetal hepatocytes via phosphoinositide-3-kinase-dependent pathway. Hepatology, 32: 528-535, 2000.
30. Pagan, R., Llobera, M., and Vilaró, S. Epithelial-mesenchymal transition in cultured neonatal hepatocytes. Hepatology, 25: 820-831, 1995.
31. Miettinen, P. J., Ebner, R., Lopez, A. R., and Derynck, R. TGF-β induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J. Cell Biol., 127: 2021-2036, 1994.
32. Caulin, C., Scholl, F. G., Frontelo, P., Gamallo, C., and Quintanilla, M. Chronic exposure of cultured transformed mouse epidermal cells to transforming growth factorβ1 induces an epithelial-mesenchymal transdifferentiaton and a spindle tumoral phenotype. Cell Growth & Differ., 6: 1027-1035, 1995.
33. Bakin, A. V., Tomlinson, A. K., Bhowmick, N. A., Moses, H. L., and Arteaga, C. L. Phosphatidylinositol 3-kinase function is required for transforming growth factor β-mediated epithelial to mesenchymal transition and cell migration. J. Biol. Chem., 47: 36803-36810, 2000.
34. Lehmann, K., Janda, E., Pierreux, C. E., Rytömaa, M., Schulze, A., McMahon, M., Hill, C. S., Beug, H., and Downward, J. Raf induces TGFβ production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells. Genes Dev., 14: 2610-2622, 2000.
35. Spagnoli, F. M., Cicchini, C., Tripodi, M., and Weiss, M. C. Inhibition of MMH (Met murine hepatocyte) cell differentiation by TGF-β is abrogated by pretreatment with the heritable differentiation effector FGFI. J. Cell Sci., 113: 3639-3647, 2000.
36. Gotzman, J., Huber, H., Thallinger, C., Wolschek, M., Jansen, B., Schulte-Hermann, R., Beug, H., and Mikulits, W. Hepatocytes convert to a fibroblastoid phenotype through the cooperation of TGF-β1 and Ha-Ras: steps towards invasiveness. J. Cell Sci., 115: 1189-1202, 2000.
37. Oft, M., Heider, K. H., and Beug, H. TGFβ signaling is necessary for carcinoma cell invasiveness and metastasis. Curr. Biol., 8: 1243-1252, 1998.
38. Piek, E., Moustakas, A., Kurisaki, A., Heldin, C. H., and ten Dijke, P. TGF(β) type 1 receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. J. Cell Sci., 112: 4557-4568, 1999.
39. Spath, G. F. and Weiss, M. C. Hepatocyte nuclear factor 4 provokes expression of epithelial marker genes, acting as morphogen in dedifferentiated hepatoma cells. J. Cell Biol., 116: 1507-1515, 1997.
40. Spath, G. F. and Weiss, M. C. Hepatocyte nuclear factor 4 expression overcomes repression of the hepatic phenotype in dedifferentiated hepatoma cells. Mol. Cell. Biol., 17: 1913-1922, 1998.
41. Spagnoli, F. M., Amicone, L., Tripodi, M., and Weiss, M. C. Identification of a bipotential precursor cell in hepatic cell lines derived from transgenic mice expressin cyto-Met in the liver. J. Cell Biol., 143: 1101-1112, 1998.
42. Bissell, D. M., Roulot, D., and George, J. Transforming growth factor β and the liver. Hepatology, 34: 859-867, 2001.
43. Shin, I., Bakin, A. V., Rodeck, U., Brunet, A., and Arteaga, C. L. Transforming growth factor β enhances epithelial cell survival via AKT-dependent regulation of FKHRL1. Mol. Biol. Cell, 12: 3328-3339, 2001.
44. Ellenrieder, V., Hendler, S. F., Boeck, W., Seufferlein, T., Menke, A., Ruhland, C., Adler, G., and Gress, T. M. Transforming growth factor β 1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res., 61: 4222-4228, 2001.
45. Janda, E., Lehmann, K., Killisch, I., Jechlinger, M., Herzig, M., Downward, J., Beug, H., and Grunert, S. Ras and TGFβ cooperatively regulate epithelial cell plasticity and metastasis: dissections of Ras signaling pathways. J. Cell Biol., 156: 299-313, 2002.
46. Franke, W. W. Separation of cytokeratin polypeptides by gel electrophoretic and chromatographic techniques and their identification by immunoblotting. Methods Enzymol., 134: 355-371, 1986.
47. Chomezynski, P. and Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem., 162: 156-159, 1987.
48. Sánchez, A., Álvarez, A. M., Pagan, R., Roncero, C., Vilaró, S., Benito, M., and Fabregat, I. Fibronectin regulates morphology, cell organization and gene expression of rat fetal hepatocytes in primary culture. J. Hepatol., 32: 242-250, 2000.