Aberrant expression of caspase cascade regulatory genes in adult T-cell leukaemia: survivin is an important determinant for prognosis

被引:78
作者
Kamihira, S
Yamada, Y
Hirakata, Y
Tomonaga, M
Sugahara, K
Hayashi, T
Dateki, N
Harasawa, H
Nakayama, K
机构
[1] Nagasaki Univ, Sch Med, Dept Lab Med, Nagasaki 8528501, Japan
[2] Nagasaki Univ, Sch Med, Dept Haematol, Nagasaki 8528501, Japan
关键词
Fas-associated phosphatase-1 (FAP-1); FLICE-inhibitory protein (FLIP); survivin; caspase-8; Fas (CD95/APO-1); ATL;
D O I
10.1046/j.1365-2141.2001.02902.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Derangement of either apoptosis or cell division is known to play an important role in tumorigenesis. Fas-mediated apoptosis on normal and leukaemic T cells is finely tuned by inhibitory proteins, such as FAP-1, FLIP and survivin, and defective caspase isoform which can attenuate the function of its intact caspase as a decoy molecule. However, complex involvement of such inhibitors in tumour biology relating to apoptotic pathology remains unclear in the neoplasms. We report the aberrant expression of FAP-1, FLIP and survivin mRNAs on leukaemic T cells from adult T-cell leukaemia (ATL) patients. Among these inhibitors, only survivin was aberrantly expressed in all ATL cases, but not in any normal peripheral blood mononuclear cells (PBMCs). Furthermore, survivin mRNA expression level was characteristic in each subtype of ATL and represented an important determinant for ATL prognosis. However, the apoptotic effector of casp-8, which is essential in Fas-mediated signal transduction, was dominant in defective casp-8 rather than intact casp-8 in ATL cells, suggesting a favourable biological situation for escape from apoptosis. Taken together, ATL cells probably possess many different regulatory mechanisms in order to attenuate Fas-mediated signalling and subsequently expand their populations under escape from apoptosis. Among these inhibitors, survivin is a useful bio-marker to assess tumour biology and may be a potential new target for apoptosis-based selective therapy in neoplasms as the expression is a general feature of neoplasia, but not normal tissues.
引用
收藏
页码:63 / 69
页数:7
相关论文
共 29 条
[1]   Anti-apoptosis gene, survivin, and prognosis of neuroblastoma [J].
Adida, C ;
Berrebi, D ;
Peuchmaur, M ;
Reyes-Mugica, M ;
Altieri, DC .
LANCET, 1998, 351 (9106) :882-883
[2]   A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma [J].
Ambrosini, G ;
Adida, C ;
Altieri, DC .
NATURE MEDICINE, 1997, 3 (08) :917-921
[3]   Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death [J].
Boldin, MP ;
Goncharov, TM ;
Goltsev, YV ;
Wallach, D .
CELL, 1996, 85 (06) :803-815
[4]   Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions [J].
Conway, EM ;
Pollefeyt, S ;
Cornelissen, J ;
DeBaere, I ;
Steiner-Mosonyi, M ;
Ong, K ;
Baens, M ;
Collen, D ;
Schuh, AC .
BLOOD, 2000, 95 (04) :1435-1442
[5]   CASH, a novel caspase homologue with death effector domains [J].
Goltsev, YV ;
Kovalenko, AV ;
Arnold, E ;
Varfolomeev, EE ;
Brodianskii, VM ;
Wallach, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (32) :19641-19644
[6]   Structure and chromosome localization of the human CASP8 gene [J].
Grenet, J ;
Teitz, T ;
Wei, T ;
Valentine, V ;
Kidd, VJ .
GENE, 1999, 226 (02) :225-232
[7]  
HORIUCHI T, 2000, BIOCHEM BIOPH RES CO, V271, P77
[8]   THE POLYPEPTIDE ENCODED BY THE CDNA FOR HUMAN CELL-SURFACE ANTIGEN FAS CAN MEDIATE APOPTOSIS [J].
ITOH, N ;
YONEHARA, S ;
ISHII, A ;
YONEHARA, M ;
MIZUSHIMA, S ;
SAMESHIMA, M ;
HASE, A ;
SETO, Y ;
NAGATA, S .
CELL, 1991, 66 (02) :233-243
[9]   Quantitative characterization and potential function of membrane Fas/APO-1 (CD95) receptors on leukaemic cells from chronic B and T lymphoid leukaemias [J].
Kamihira, S ;
Yamada, Y ;
Hirakata, Y ;
Tsuruda, K ;
Sugahara, K ;
Tomonaga, M ;
Maeda, T ;
Tsukasaki, K ;
Atogami, S ;
Kobayashi, N .
BRITISH JOURNAL OF HAEMATOLOGY, 1997, 99 (04) :858-865
[10]   Discrepant expression of membrane and soluble isoforms of Fas (CD95/APO-1) in adult T-cell leukaemia: soluble Fas isoform is an independent risk factor for prognosis [J].
Kamihira, S ;
Yamada, Y ;
Tomonaga, M ;
Sugahara, K ;
Tsuruda, K .
BRITISH JOURNAL OF HAEMATOLOGY, 1999, 107 (04) :851-860