Expression patterns of inhibitor of apoptosis proteins in malignant pleural mesothelioma
Saturday, January 27th, 2007.
The Journal of Pathology. 2007 Mar;211(4):447-54. [Link]
GJ Gordon 1 *, M Mani 1, L Mukhopadhyay 1, L Dong 1, HR Edenfield 1, JN Glickman 2, BY Yeap 3, DJ Sugarbaker 1, R Bueno 1
1The Thoracic Surgery Oncology Laboratory and the Division of Thoracic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
2Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
3Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
email: GJ Gordon (ggordon@partners.org)
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.
Glossary
- prognosis
- (prog-no-sis) a prediction of the course of disease; the outlook for the cure of the patient. For example, women with breast cancer that was detected early and who received prompt treatment have a good prognosis.
- oncology
- (on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.
- nucleus
- (new-clee-us) the center of a cell where the DNA is housed and replicated. Studying the size and shape of a cell's nucleus under the microscope can help pathologists distinguish cancer cells from benign cells.
- gene
- a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Women who have BRCA1 or BRCA2 gene mutations (defects) have an inherited tendency to develop breast cancer.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- tissue
- a collection of cells, united to perform a particular function.
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
- apoptosis
- a type of cell death in which the cell basically commits suicide; scientists believe some types of cancer may originate from an interruption of this programmed cell death, allowing cells to grow out of control.
