Targets of c-Jun NH(2)-terminal kinase 2-mediated tumor growth regulation revealed by serial analysis of gene expression.
Although the c-Jun NH(2)-terminal kinase (JNK) pathway has been implicated in mediating cell growth and transformation, its downstream effectors remain to be identified. Using JNK2 antisense oligonucleotides (JNK2AS), we uncovered previously a role for JNK2 in regulating cell cycle progression and survival of human PC3 prostate carcinoma cells. Here, to identify genes involved in implementing JNK2-mediated effects, we have analyzed global gene expression changes in JNK2-deprived PC3 cells using Serial Analysis of Gene Expression. More than 40,000 tags each were generated from control and PC3-JNK2AS libraries, corresponding to 15,999 and 20,698 unique transcripts, respectively. Transcripts corresponding to transcription factors, stress-induced genes, and apoptosis-related genes were up-regulated in the PC3-JNK2AS library, revealing a significant stress response after the inhibition of JNK2 expression. Genes involved in DNA repair, mRNA turnover, and drug resistance were found to be down-regulated by inhibition of JNK2 expression, further highlighting the importance of JNK2 signaling in regulating cell homeostasis and tumor cell growth.
Potapova
Olga
O
Cell Stress and Aging Section, Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging-IRP/NIH, Baltimore, MD 21224, USA.
Anisimov
Sergey V
SV
Gorospe
Myriam
M
Dougherty
Ryan H
RH
Gaarde
William A
WA
Boheler
Kenneth R
KR
Holbrook
Nikki J
NJ
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology
D016376:Oligonucleotides, Antisense; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases