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Expression patterns of inhibitor of apoptosis proteins in malignant pleural mesothelioma
Author(s) -
Gordon GJ,
Mani M,
Mukhopadhyay L,
Dong L,
Edenfield HR,
Glickman JN,
Yeap BY,
Sugarbaker DJ,
Bueno R
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2121
Subject(s) - xiap , survivin , inhibitor of apoptosis , cancer research , biology , tissue microarray , apoptosis , mesothelioma , programmed cell death , cancer , medicine , pathology , caspase , genetics
Abstract Inhibitor of apoptosis proteins (IAPs) comprise a family of structurally similar proteins, five of which are widely studied in the context of cancer: IAP‐1/MIHC/cIAP2, IAP‐2/MIHB/cIAP1, livin/ML‐IAP/KIAP, survivin, and XIAP/MIHA/hILP. IAPs are overexpressed by most neoplasms, promote tumour cell survival after a wide variety of apoptotic stimuli, and frequently have gene and/or protein expression patterns associated with a relatively poor prognosis. However, many IAPs are also expressed by normal tissues, can facilitate apoptotic cell death, and have expression patterns associated with a relatively favourable prognosis in some cases. The result is that the precise role(s) of IAPs in human tumours is not exactly known. It has been previously reported that IAP‐1 is overexpressed in malignant pleural mesothelioma (MPM) and is responsible for a large degree of the resistance of cultured MPM cells to cisplatin. Given the high homology of IAP family members, it is likely that other IAPs will be important in MPM. In the present study, the gene and protein expression patterns of IAP‐1, IAP‐2, survivin, livin, and XIAP have been determined in MPM cell lines ( n = 9) and a large number of MPM tumours using high‐density oligonucleotide microarrays ( n = 40) and an MPM tissue array ( n = 66). Human tumours were linked to clinical data and it was found that IAP‐1 and survivin mRNA expression patterns were associated with a relatively shorter patient survival, while those of XIAP and livin were associated with a relatively longer patient survival. Abundant protein for all IAPs was also detected in MPM tumours, where they were expressed primarily in the cytoplasm. Only IAP‐1 and livin protein was expressed in the nucleus of MPM tumours. These results provide the rationale for additional study of this gene family in MPM and cancer in general. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.