Abstract
The BCL-6 proto-oncogene encodes a 92- to 98-kDa transcriptional repressor containing the BTB/POZ domain at its N-terminal region and the zinc finger domain at its C-terminal region, respectively. In the present study, we examined the function of BCL-6 by using a recombinant adenovirus expressing BCL-6 (Ax1CA-BCL-6) and the lacZ reporter gene (Ax1CA-lacZ). Viability of CV-1 and HeLa cells infected with Ax1CA-BCL-6 was markedly reduced due to apoptosis, suggesting that BCL-6-overexpression induces apoptosis in CV-1 and HeLa cells. FACS analysis revealed that BCL-6-overexpressing cells are accumulated not only at the sub-G1 but also at G2/M phase. Induction of apoptosis by BCL-6 was preceded by down-regulation of apoptosis repressors BCL-2 and BCL-XL. These results suggest that BCL-6 induces apoptosis by regulating the expression of these apoptosis-regulating genes.
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References
Albagli O, Dhordain P, Deweindt C, Lecocq G and Leprince D. . 1995 Cell Growth & Differ. 6: 1193–1198.
Albagli O, Dhordain P, Bernardin F, Quief S, Kerkaert JP and Leprince D. . 1996 Biochem. Biophys. Res. Commun. 220: 911–915.
Allman D, Jain A, Dent A, Maile RR, Selvaggi T, Kehry MR and Staudt LM. . 1996 Blood 87: 5257–5268.
Bardwell VJ and Treisman R. . 1994 Genes & Dev. 8: 1664–1677.
Baron BW, Stanger RR, Hume E, Sadhu A, Mick R, Kerckaert JP, Deweindt C, Bastard C, Nucifora G, Zeleznik LN and McKeithan TW. . 1995 Genes, Chrom. & Cancer 13: 221–224.
Bastard CC, Deweindt C, Kerckaert JP, Lenormand B, Rossi A, Pezzella F, Fruchart C, Duval C, Monconduit M and Tilly H. . 1994 Blood 83: 2423–2427.
Cattoretti G, Chang CC, Cechova K, Zhang J, Ye BH, Falini B, Louie DC, Offit K, Chaganti RS and Dalla-Favera R. . 1995 Blood 86: 45–53.
Chang CC, Ye BH, Chaganti RS and Dalla-Favera R. . 1996 Proc. Natl. Acad. Sci. USA 93: 6947–6952.
Choi MSK, Boise LH, Gottschalk AR, Quintans J, Thompson CB and Klaus GGB. . 1995 Eur. J. Immunol. 25: 1352–1357.
Darzynkiewicz Z, Bruno S, Del BG, Gorczyca W, Hotz MA, Lassota P and Traganos F. . 1992 Cytometry 13: 795–808.
Dent AL, Shaffer AL, Yu X, Allman D and Staudt LM. . 1997 Science 276: 589–592.
Deweindt C, Albagli O, Bernardin F, Dhordain P, Quief S, Lantoine D, Kerckaert JP and Leprince D. . 1995 Cell Growth & Differ. 6: 1495–1503.
Dhordain P, Albagli O, Ansieau S, Koken MH, Deweindt C, Quief S, Lantoine D, Leutz A, Kerckaert JP and Leprince D. . 1995 Oncogene 11: 2689–2697.
Fan S, Smith ML, Rivet II DJ, Duba D, Zhan Q, Kohn KW, Fornace Jr AJ and O'Connor PM. . 1995 Cancer Res. 55: 1649–1654.
Fukuda T, Yoshida T, Okada S, Hatano M, Miki T, Ishibashi K, Okabe S, Koseki H, Hirosawa S, Taniguchi M, Miyasaka N and Tokuhisa T. . 1997 J. Exp. Med. 186: 439–448.
Ghia P, Boussiotis VA, Schultze JL, Cardoso AA, Dorfman DM, Gribben JG, Freedman AS and Nadler LM. . 1998 Blood 91: 244–251.
Ishida T, Kobayashi N, Tojo T, Ishida S, Yamamoto T and Inoue J. . 1995 J. Immunol. 155: 5527–5535.
Kanegae Y, Makimura M and Saito I. . 1994 Jpn. J. Med. Sci. Biol. 47: 157–166.
Kanegae Y, Lee G, Sato Y, Tanaka M, Nakai M, Sakaki T, Sugano S and Saito I. . 1995 Nucl. Acid. Res. 23: 3816–3821.
Kawamata N, Miki T, Ohashi K, Suzuki K, Fukuda T, Hirosawa S and Aoki N. . 1994 Biochem. Biophys. Res. Comm. 204: 366–374.
Kerckaert JP, Deweindt C, Tilly H, Quief S, Lecocq G and Bastard C. . 1993 Nature Genet. 5: 66–70.
Liu YJ, Mason DY, Johonson GD, Abbot S, Gregory CD, Hardie DL, Gordon J and MacLennan ICM. . 1991 Eur. J. Immunol. 21: 1905–1910.
Liu YJ and Arpin C. . 1997 Germinal center development: Immunological Reviews. Parham P. (ed.).. Munksgaard: Copenhagen Vol. 156.: pp. 111–126.
Lo CF, Ye BH, Lista F, Corradini P, Offit K, Knowles DM, Chaganti RS and Dalla-Favera R. . 1994 Blood 83: 1757–1759.
Martinez-Valdez H, Guret C, de BO, Fugier I, Banchereau J and Liu YJ. . 1996 J. Exp. Med. 183: 971–977.
Migliazza A, Martinotti S, Chen W, Fusco C, Ye BH, Knowles DM, Offit K, Chaganti RS and Dalla-Favera R. . 1995 Proc. Natl. Acad. Sci. USA 92: 12520–12524.
Miki T, Kawamata N, Hirosawa S and N Aoki. . 1994 Blood 83: 26–32.
Miyake S, Makimura M, Kanegae Y, Harada S, Sato Y, Takamori K, Tokuda C and Saito I. . 1996 Proc. Natl. Acad. Sci. USA 93: 1320–1324.
Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B and Reed JC. . 1994 Oncogene 9: 1799–1805.
Moriyama M, Yamochi T, Semba K, Akiyama T and Mori S. . 1997 Oncogene 14: 2465–2474.
Niwa H, Yamamura K and Miyazaki J. . 1991 Gene 108: 193–199.
Offit K, Lo CF, Louie DC, Parsa NZ, Leung D, Portlock C, Ye BH, Lista F, Filippa DA, Rosenbaum A, Ladanyi M, Jhanwar S, Dalla-Favera R and Chaganti RSK. . 1994 New Engl. J. Med. 331: 74–80.
Oltvai ZN, Milliman CL and Korsmeyer SJ. . 1993 Cell 74: 609–619.
Onizuka T, Moriyama M, Yamochi T, Kuroda T, Kazama A, Kanazawa N, Sato K, Kato T, Ota H and Mori S. . 1995 Blood 86: 28–37.
Seto M, Jaeger U, Hockett RD, Graninger W, Bennett S, Goldman P and Korsmeyer SJ. . 1988 EMBO J. 7: 123–131.
Seyfert VL, Allman D, He Y and Staudt LM. . 1996 Oncogene 12: 2331–2342.
Tsubata T, Wu J and Honjo T. . 1993 Nature 364: 645–648.
Tuscano JM, Druey TK, Riva A, Pena J, Thompson CB and Kehrl H. . 1996 Blood 88: 1359–1364.
Ye BH, Lista F, Lo CF, Knowles DM, Offit K, Chaganti RS and Dalla-Favera R. . 1993 Science 262: 747–750.
Ye BH, Chaganti S, Chang CC, Niu H, Corradini P, Chaganti RS and Dalla-Favera R. . 1995 EMBO J. 14: 6209–6217.
Ye BH, Cattoretti G, Shen Q, Zhang J, Hawe N, de WR, Leung C, Nouri SM, Orazi A, Chaganti RS, Rothman P, Stall AM, Pandolfi PP and Dalla-Favera R. . 1997 Nature Genet. 16: 161–170.
Acknowledgements
We thank to Dr Junichiro Inoue for provision of bcl-XL cDNA and also thank to Dr Yoshihide Tsujimoto for provision of bcl-2 cDNA. We thank to Dr Masao Seto for provision of plasmid DNA containing 5′-flanking region of bcl-2 gene. We thank to Dr Izum Saito for helpful suggestions and discussion on generating the recombinant adenoviruses, and also thank to him for provision of pAdex1CAwt cassette cosmid DNA.
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Yamochi, T., Kaneita, Y., Akiyama, T. et al. Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death accompanied by down-regulation of BCL-2 and BCL-XL. Oncogene 18, 487–494 (1999). https://doi.org/10.1038/sj.onc.1202334
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DOI: https://doi.org/10.1038/sj.onc.1202334
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