Suppression of activin-induced apoptosis by novel antisense strategy in human prostate cancer cells.
Apoptosin, a novel gene encoding a mitotic kinase-motif protein, is stimulated by activin, a member of TGF-beta family, in human LNCaP prostate cancer cells and in patient tissues. We employed a gene knockout methodology based on the covalent bonding of chemically modified antisense probes to apoptosin mRNAs in LNCaP cells. The mRNA-antisense hybrid duplexes were neither translated nor post-transcriptionally modified, resulting in no protein synthesis. Introducing antisense apoptosin into activin-induced apoptotic LNCaP cells prevented apoptosis, interfered with genomic DNA fragmentation and released cell cycle checkpoint. These findings suggest that the apoptosin, in addition to p53, is important in apoptotic regulation of human prostate cancers.
Ying
S Y
SY
Department of Cell and Neurobiology, University of Southern California, School of Medicine, BMT-401, 1333 San Pablo Street, Los Angeles, California, 90033, USA. sying@hsc.usc.edu
Chuong
C M
CM
Lin
S
S
D028341:Activins; D016375:Antisense Elements (Genetics); D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D015870:Gene Expression; D018390:Gene Targeting; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D008297:Male; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011494:Protein Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D016375:Antisense Elements (Genetics); D012333:RNA, Messenger; D028341:Activins; D007265:Inhibins; D011494:Protein Kinases