Inhibitors of apoptosis proteins in prostate cancer cell lines.
BACKGROUND
The caspases are the central executioners of apoptosis. The inhibitors of apoptosis proteins (IAPs) are a family of recently described caspase inhibitors. We hypothesised that tumor resistance to apoptosis could be due in part to IAP expression.


METHODS
The expression of NAIP, cIAP-1, cIAP-2, XIAP, and survivin was investigated in the prostate cancer cell lines LNCaP, PC3, and DU145. RNase protection assays and Western blotting were used to assess RNA and protein expression. Apoptotic susceptibility was determined using etoposide and assessed by propidium iodide (PI) DNA incorporation using flow cytometry.


RESULTS
DU145 and PC3 cells were more resistant to apoptosis than LNCaP cells. All the IAPs were identified in the cell lines with variation in IAP expression between different cell types. Immunohistochemistry demonstrated cIAP-1 expression in PC3 cells was nuclear, while the expression of cIAP-2 and XIAP was perinuclear. Growing LNCaP cells in charcoal-stripped or androgen-supplemented medium resulted in no alteration in IAP expression.


CONCLUSIONS
This study characterises the expression of IAP in three of the most commonly used prostate cancer cells. IAP may make an important contribution to apoptotic resistance in patients with prostate cancer.
McEleny
Kevin R
KR
Department of Surgery, Mater Misericordiae Hospital, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, 47 Eccles Street, Dublin 7, Ireland.
Watson
R William G
RW
Coffey
Ronan N T
RN
O'Neill
Amanda J
AJ
Fitzpatrick
John M
JM
D017209:Apoptosis / Q000235:genetics* / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis; D015853:Cysteine Proteinase Inhibitors / Q000032:analysis; D004791:Enzyme Inhibitors / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D051616:Neuronal Apoptosis-Inhibitory Protein; D011471:Prostatic Neoplasms / Q000473:pathology*; D014176:Protein Biosynthesis; D011506:Proteins; D000077022:Survivin; D014407:Tumor Cells, Cultured; D051636:X-Linked Inhibitor of Apoptosis Protein
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; C496800:NAIP protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D011506:Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human