Abstract
Caspase-7 is a caspase involved in the execution phase of apoptosis. To explore the possibility that the genetic alterations of CASPASE-7 might be involved in the development of human cancers, we analysed the entire coding region and all splice sites of human CASPASE-7 gene for the detection of somatic mutations in a series of human solid cancers, including carcinomas from stomach, colon, head/neck, esophagus, urinary bladder and lung. Overall, we detected CASPASE-7 mutations in two of 98 colon carcinomas (2.0%), one of 50 esophageal carcinomas (2.0%) and one of 33 head/neck carcinomas (3.0%). We expressed the tumor-derived caspase-7 mutants in 293 T cells and found that the apoptosis was reduced compared to the wild-type caspase-7. This is the first report on the CASPASE-7 gene mutations in human malignancies, and our data suggest that the inactivating mutations of the CASPASE-7 gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human solid cancers.
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Abbreviations
- PCR:
-
polymerase chain reaction
- DAPI:
-
4′, 6-diamidine-2′-phenylindole dihydrochloride
- GFP:
-
green fluorescent protein
- SSCP:
-
single strand conformation polymorphism
- LOH:
-
loss of heterozygosity
- TRAIL:
-
tumor necrosis factor-related apoptosis-inducing ligand
References
Boldin MP, Goncharov TM, Goltsev YV and Wallach D . (1996). Cell, 2, 803–815.
Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y and Dataa P . (2001). Cell, 104, 769–780.
Duan H, Chinnaiyan AM, Hudson PL, Wing JP, He WW and Dixit VM . (1996). J. Biol. Chem., 271, 1621–1625.
Fulda S, Kufer MU, Meyer E, van Valen F, Dockhorn-Dworniczak B and Debatin KM . (2001). Oncogene, 20, 5865–5877.
Hanahan D and Weinberg RA . (2000). Cell, 100, 57–70.
Hirata H, Takahashi A, Kobayashi S, Yonehara S, Sawai H, Okazaki T, Yamamoto K and Sasada MJ . (1998). J. Exp. Med., 187, 587–600.
Krawczak M, Reiss J and Cooper DN . (1992). Hum. Genet., 90, 41–54.
Kurokawa H, Nishio K, Fukumoto H, Tomonari A, Suzuki T and Saijo N . (1999). Oncol. Rep., 6, 33–37.
Lee JY, Dong SM, Kim SY, Yoo NJ, Lee SH and Park WS . (1998). Virchows. Arch., 433, 305–309.
Lee SH, Shin MS, Park WS, Kim SY, Kim HS, Han JY, Park GS, Dong SM, Pi JH, Kim CS, Kim SH, Lee JY and Yoo NJ . (1999). Oncogene, 18, 3754–3760.
Lippke JA, Gu Y, Sarnecki C, Caron PR and Su MS . (1996). J. Biol. Chem., 271,1825–1828.
Mandruzzato S, Brasseur F, Andry G, Boon T and van der Bruggen PA . (1997). J. Exp. Med., 186, 785–793.
Mitelman F, Mertens F and Johansson B . (1997). Nat. Genet., 15, 417–474.
Mollenhauer J, Herbertz S, Helmke B, Kollender G, Krebs I, Madsen J, Holmskov U, Sorger K, Schmitt L, Wiemann S, Otto HF, Grone HJ and Poustka A . (2001). Cancer Res., 61, 8880–8886.
Nicholson DW . (1999). Cell Death Differ., 6, 1028–1042.
Pai JT, Brown MS and Goldstein JL . (1996). Proc. Natl. Acad. Sci. USA, 93, 5437–5442.
Palmerini F, Devilard E, Jarry A, Birg F and Xerri L . (2001). Hum. Pathol., 32, 461–467.
Reed JC . (2000). Am. J. Pathol., 39, 1415–1430.
Schwartz Jr S, Yamamoto H, Navarro M, Maestro M, Reventos J and Perucho M . (1999). Cancer Res., 59, 2995–3002.
Shin MS, Kim HS, Kang CS, Park WS, Kim SY, Lee SN, Lee JH, Park JY, Jang JJ, Kim CW, Kim SH, Lee JY, Yoo NJ and Lee SH . (2002). Blood, 99, 4094–4099.
Shin MS, Park WS, Kim SY, Kanf SJ, Song KY, Park JY, Dong SM, Pi JH, Oh RR, Lee JY, Yoo NJ and Lee SH . (1999). Am. J. Pathol., 154, 1785–1791.
Slee EA, Adrain C and Martin SJ . (2001). J. Biol. Chem., 276, 7320–7326.
Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR and Martin SJ . (1999). J. Cell Biol., 144, 281–292.
Teitz T, Wei T, Valentine MB, Vanin EF, Grenet J, Valentine VA, Behm FG, Look AT, Lahti JM and Kidd VJ . (2000). Nat. Med., 6, 529–535.
Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS and Dixit VM . (1995). Cell, 81, 801–819.
Zörnig M, Grzeschiczek A, Kowalski MB, Hartmann KU and Möröy T . (1995). Oncogene, 10, 2397–2401.
Acknowledgements
This study was supported by funding from the 21C Frontier Functional Human Genome Project from the Ministry of Science and Technology of Korea (M101KB010001-02K0201-03710).
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Soung, Y., Lee, J., Kim, H. et al. Inactivating mutations of CASPASE-7 gene in human cancers. Oncogene 22, 8048–8052 (2003). https://doi.org/10.1038/sj.onc.1206727
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DOI: https://doi.org/10.1038/sj.onc.1206727
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