Abstract
Objective: Smad7 was identified as a TGF-β-inducible antagonist of TGF-β signaling and might participate in a negative feedback loop to control TGF-β signaling. In this study, the responsiveness of Smad7 to TGF-β1 was examined in the BEP2D and BERP35T-2 cells to investigate the possible mechanism of Smad7 in the tumorigenesis. Methods: Northern and western blot were performed to exam the Smad7 and TGF-β1 expression abundance in BEP2D and BERP35T-2 at both transcription and translation level. Results: The expression level of Smad7 mRNA in BERP35T-2 cells was higher than that in BEP2D cells. When stimulated with TGF-β1, Smad7 expression was up-regulated evidently in BEP2D cells, but not significantly in BERP35T-2 cells. The abundance of TGF-β1 in the cytoplasm of BERP35T-2 was not significantly higher than in BEP2D (P>0.05); whereas the abundance of TGF-β1 in BERP35T-2 cell culture medium was significantly higher than in BEP2D cell culture medium (P<0.05). Conclusion: Over expression of Smad7 mRNA and down-regulation of the cells’ responsiveness to TGF-β1 in human lung cancer cell line might be involved in lung carcinogenisis.
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References
Roberts AB. TGF-beta signaling from receptors to the nucleus [J]. Microbes Infect 1999; 15:1265.
Wrana JL, Attisano L, Wieser R, et al. Mechanism of activation of the TGF-beta receptor [J]. Nature 1994; 370:341.
Massague J. TGF-beta signal transduction [J]. Annu Rev Biochem 1998; 67:753.
Heldin CH, Miyazono K, Dijke PT. TGF-beta signaling from cell membrane to nucleus through SMAD proteins [J]. Nature 1997; 390:465.
Miyazono K. TGF-beta signaling by Smad proteins [J]. Cytokine Growth Factor Rev 2000; 11:15.
Wrana JL. Regulation of Smad activity [J]. Cell 2000; 100:189.
Itoh SM, Landstrom A, Hermansson F, et al. Transforming growth factor 1 induces nuclear export of inhibitory Smad7 [J]. J Biol Chem 1998; 273:29195.
Afrakhte M, Moren A, Jossan S, et al. Induction of inhibitory Smad6 and Smad7 mRNA by TGF-β family members [J]. Biochem Biophys Res Commun 1998; 249:505.
Ishisaki A, Yamato K, Nakao A, et al. Smad7 is an activin-inducible inhibitor of activin-induced growth arrest and apoptosis in mouse B cells [J]. J Biol Chem 1998; 273:24293.
Attisano JL, Wrana F, López-Casillas, et al. TGF-receptors and actions [J]. Biochim. Biophys Acta 1994; 1222:71.
Derynck R, Feng XH. TGF- receptor signaling [J]. Biochim Biophys Acta 1997; 1333:F105.
Hayashi HS, Abdollah Y, Qiu J, et al. The MAD-related protein Smad7 associates with the TGF- receptor and functions as an antagonist of TGF signaling [J]. Cell 1997; 89:1165.
Nakao AM, Afrakhte A, Morén T, et al. Identification of Smad7-α TGF- inducible antagonist of TGF- signaling [J]. Nature 1997; 389:631.
Souchelnytskyi ST, Nakayama A, Nakao A, et al. Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-receptors [J]. J Biol Chem 1998; 273:25364.
Markowitz S, Wang J, Meyeroff L, et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability [J]. Science 1995; 268:1336.
Venkatasubbarao K, Ahmed MM, Swiderski C, et al. Novel mutations in the polyadenine tract of the transforming growth factor beta type II receptor gene are found in a subpopulation of human pancreatic adenocarcinomas [J]. Genes Chromosomes Cancer 1998; 22:138.
Goggins M, Shekher M, Tumacioglu K, et al. Genetic alterations of the transforming growth factor beta receptor genes in pancreatic and biliary adenocarcinomas [J]. Cancer Res 1998; 58:5329.
DeCoteau JF, Knaus PI, Yankelev H, et al. Loss of functional cell surface transforming growth factor beta (TGF-beta) type I receptor correlates with insensitivity to TGF-beta in chronic lymphocytic leukemia [J]. Proc Natl Acad Sci USA 1997; 94:5877.
Kleeff J, Ishiwata T, Maruyama H, et al. The TGF-β signaling inhibitor Smad7 enhances tumorigenicity in pancreatic cancer [J]. Oncogene 1999; 18:5363.
Stopa M, Anhuf D, Terstege L, et al. Participation of Smad2, Smad3, and Smad4 in Transforming Growth Factor β (TGF-β)-induced Activation of Smad7 [J]. J Biol Chem 2000; 275:29308.
Baldwin RL, Friess H, Yokoyama M, et al. Attenuated ALK5 receptor expression in human pancreatic cancer: correlation with resistance to growth inhibition [J]. Int J Cancer 1996; 67:283.
Hahn SA, Schutte M, Hoque AT, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1 [J]. Science 1996; 271:350.
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Foundation item: This work was supported by the National “973” Key Basic Research Program of China (No. G1998051207).
Biography: HUO Yan-ying (1973–), female, candidate for doctor of medicine, Beijing Institute of Radiation Medicine, majors in molecular toxicology.
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Huo, Yy., Zhang, Kt., Li, By. et al. Responsiveness of Smad7 gene to TGF-β1 in the tumorigenesis. Chin. J. Cancer Res. 14, 170–174 (2002). https://doi.org/10.1007/s11670-002-0038-z
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DOI: https://doi.org/10.1007/s11670-002-0038-z