Abstract
To identify genes which overexpression results into chromosomal instability (CIN), we developed a biological approach based on a yeast indicator strain in which CIN can be detected by a sectoring phenotype. Screening in this strain of a yeast genomic library cloned into a high copy vector led us to identify, among the clones generating 100% of sectoring colonies, Clb5, one of the six B-type cyclins present in yeast. Overexpression of cyclin B2 and cyclin B1, the two human homologs of Clb5, in the CIN indicator strain resulted also into a sectoring phenotype and induced, like overexpression of Clb5, an abnormal sensitivity to benomyl, indicating that overexpression of B-type cyclins alters the spindle checkpoint. In a series of 38 primary colorectal cancers, we detected in five tumors (13%) an accumulation of cyclin B1, which was neither related to mRNA overexpression nor to mutation within the coding region, and in five other tumors (13%) a 2–10-fold increase of cyclin B2 mRNA which was not related to gene amplification. These results suggest that overexpression of cyclins B, resulting from different mechanisms, could contribute, through an alteration of the spindle checkpoint, to the chromosomal instability observed in cancer.
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References
Amon A . 1999 Curr. Opin. Genet. Dev. 9: 69–75
Brandeis M, Rosewell I, Carrington M, Crompton T, Jacobs MA, Kirk J, Gannon J, Hunt T . 1998 Proc. Natl. Acad. Sci. USA 95: 4344–4349
Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B . 1998 Nature 392: 300–303
Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C . 1999 Genomics 58: 181–187
Connelly C, Hieter P . 1996 Cell 86: 275–285
Draviam VM, Orrechia S, Lowe M, Pardi R, Pines J . 2001 J. Cell. Biol. 152: 945–958
Fodde R, Kuipers J, Rosenberg C, Smits R, Kielman M, Gaspar C, van Es JH, Breukel C, Wiegant J, Giles RH, Clevers H . 2001 Nat. Cell. Biol. 3: 433–438
Hauf S, Waizenegger IC, Peters JM . 2001 Science 293: 1320–1323
Heaney AP, Singson R, McCabe CJ, Nelson V, Nakashima M, Melmed S . 2000 Lancet 355: 716–719
Hyland KM, Kingsbury J, Koshland D, Hieter P . 1999 J. Cell. Biol. 145: 15–28
Ito H, Fukuda Y, Murata K, Kimura A . 1983 J. Bacteriol. 153: 163–168
Jackman M, Firth M, Pines J . 1995 EMBO J. 14: 1646–1654
Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Nathke IS . 2001 Nat. Cell. Biol. 3: 429–432
Koshland D, Hieter P . 1987 Methods Enzymol. 155: 351–372
Kotani T, Yoshida N, Mita K, Yamashita M . 2001 Mol. Reprod. Dev. 59: 199–208
Lengauer C, Kinzler KW, Vogelstein B . 1997 Nature 386: 623–627
Lengauer C, Kinzler KW, Vogelstein B . 1998 Nature 396: 643–649
Manni I, Mazzaro G, Gurtner A, Mantovani R, Haugwitz U, Krause K, Engeland K, Sacchi A, Soddu S, Piaggio G . 2001 J. Biol. Chem. 276: 5570–5576
Michel LS, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W, Dobles M, Sorger PK, Murty VV, Benezra R . 2001 Nature 409: 355–359
Minshull J, Blow JJ, Hunt T . 1989 Cell 56: 947–956
Minshull J, Golsteyn R, Hill CS, Hunt T . 1990 EMBO J. 9: 2865–2875
Mumberg D, Muller R, Funk M . 1994 Nucleic Acids Res. 22: 5767–5768
Ohsumi K, Sawada W, Kishimoto T . 1994 J. Cell Sci. 107: 3005–3013
Pines J, Hunter T . 1989 Cell 58: 833–846
Segal M, Clarke DJ, Reed SI . 1998 J. Cell Biol. 143: 135–145
Shirayama M, Toth A, Galova M, Nasmyth K . 1999 Nature 402: 203–207
Soria JC, Jang SJ, Khuri FR, Hassan K, Liu D, Hong WK, Mao L . 2000 Cancer Res. 60: 4000–4004
Spruck CH, Won KA, Reed SI . 1999 Nature 401: 297–300
Tsukasaki K, Miller CW, Greenspun E, Eshaghian S, Kawabata H, Fujimoto T, Tomonaga M, Sawyers C, Said JW, Koeffler HP . 2001 Oncogene 20: 3301–3305
Wang A, Yoshimi N, Ino N, Tanaka T, Mori H . 1997 J. Cancer Res. Clin. Oncol. 123: 124–127
Yin XY, Grove L, Datta NS, Katula K, Long MW, Prochownik EV . 2001 Cancer Res. 61: 6487–6493
Zou H, McGarry TJ, Bernal T, Kirschner MW . 1999 Science 285: 418–422
Acknowledgements
This work was supported by l'Association pour la Recherche sur le Cancer and La Fondation pour la Recherche Médicale.
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Sarafan-Vasseur, N., Lamy, A., Bourguignon, J. et al. Overexpression of B-type cyclins alters chromosomal segregation. Oncogene 21, 2051–2057 (2002). https://doi.org/10.1038/sj.onc.1205257
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DOI: https://doi.org/10.1038/sj.onc.1205257
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