Abstract
Background/Aims: The FRA16D fragile site gene WWOX is a tumor suppressor that participates in p53-mediated apoptosis. The c-jun N-terminal kinase JNK1 interacts with WWOX and inhibits apoptosis. We investigated the function of WWOX in human hepatocellular carcinoma (HCC) and the effect of JNK inhibition on WWOX-mediated apoptosis. Methods: Allelic imbalance on chromosome 16 was analyzed in 73 HCCs using 53 microsatellite markers. WWOX mRNA in HCC cell lines and primary HCCs was measured by real-time RT-PCR. Effects of WWOX on proliferation and apoptosis and the interaction between WWOX and JNK inhibition were examined. Results: Loss on chromosome 16 occurred in 34 of 73 HCCs. Of 11 HCC cell lines, 2 had low, 7 intermediate, and 2 had high WWOX mRNA. Of 51 primary tumors, 23 had low WWOX mRNA. Forced expression of WWOX in SNU387 cells decreased FGF2-mediated proliferation and enhanced apoptosis induced by staurosporine and the JNK inhibitor SP600129. Conversely, knockdown of WWOX in SNU449 cells using shRNA targeting WWOX increased proliferation and resistance to SP600129-induced apoptosis. Conclusions: WWOX induces apoptosis and inhibits human HCC cell growth through a mechanism enhanced by JNK inhibition.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 373-383 |
| Number of pages | 11 |
| Journal | Journal of Hepatology |
| Volume | 49 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2008 |
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Keywords
- Apoptosis
- Hepatocellular carcinoma
- JNK
- WWOX
ASJC Scopus subject areas
- Gastroenterology
Cite this
The JNK inhibitor SP600129 enhances apoptosis of HCC cells induced by the tumor suppressor WWOX. / Aderca, Ileana; Moser, Catherine D.; Veerasamy, Manivannan; Bani-Hani, Ahmad H.; Bonilla-Guerrero, Ruben; Ahmed, Kadra; Shire, Abdirashid; Cazanave, Sophie C.; Montoya, Damian P.; Mettler, Teresa A.; Burgart, Lawrence J.; Nagorney, David M.; Thibodeau, Stephen N; Cunningham, Julie M; Lai, Jin Ping; Roberts, Lewis Rowland.
In: Journal of Hepatology, Vol. 49, No. 3, 09.2008, p. 373-383.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The JNK inhibitor SP600129 enhances apoptosis of HCC cells induced by the tumor suppressor WWOX
AU - Aderca, Ileana
AU - Moser, Catherine D.
AU - Veerasamy, Manivannan
AU - Bani-Hani, Ahmad H.
AU - Bonilla-Guerrero, Ruben
AU - Ahmed, Kadra
AU - Shire, Abdirashid
AU - Cazanave, Sophie C.
AU - Montoya, Damian P.
AU - Mettler, Teresa A.
AU - Burgart, Lawrence J.
AU - Nagorney, David M.
AU - Thibodeau, Stephen N
AU - Cunningham, Julie M
AU - Lai, Jin Ping
AU - Roberts, Lewis Rowland
PY - 2008/9
Y1 - 2008/9
N2 - Background/Aims: The FRA16D fragile site gene WWOX is a tumor suppressor that participates in p53-mediated apoptosis. The c-jun N-terminal kinase JNK1 interacts with WWOX and inhibits apoptosis. We investigated the function of WWOX in human hepatocellular carcinoma (HCC) and the effect of JNK inhibition on WWOX-mediated apoptosis. Methods: Allelic imbalance on chromosome 16 was analyzed in 73 HCCs using 53 microsatellite markers. WWOX mRNA in HCC cell lines and primary HCCs was measured by real-time RT-PCR. Effects of WWOX on proliferation and apoptosis and the interaction between WWOX and JNK inhibition were examined. Results: Loss on chromosome 16 occurred in 34 of 73 HCCs. Of 11 HCC cell lines, 2 had low, 7 intermediate, and 2 had high WWOX mRNA. Of 51 primary tumors, 23 had low WWOX mRNA. Forced expression of WWOX in SNU387 cells decreased FGF2-mediated proliferation and enhanced apoptosis induced by staurosporine and the JNK inhibitor SP600129. Conversely, knockdown of WWOX in SNU449 cells using shRNA targeting WWOX increased proliferation and resistance to SP600129-induced apoptosis. Conclusions: WWOX induces apoptosis and inhibits human HCC cell growth through a mechanism enhanced by JNK inhibition.
AB - Background/Aims: The FRA16D fragile site gene WWOX is a tumor suppressor that participates in p53-mediated apoptosis. The c-jun N-terminal kinase JNK1 interacts with WWOX and inhibits apoptosis. We investigated the function of WWOX in human hepatocellular carcinoma (HCC) and the effect of JNK inhibition on WWOX-mediated apoptosis. Methods: Allelic imbalance on chromosome 16 was analyzed in 73 HCCs using 53 microsatellite markers. WWOX mRNA in HCC cell lines and primary HCCs was measured by real-time RT-PCR. Effects of WWOX on proliferation and apoptosis and the interaction between WWOX and JNK inhibition were examined. Results: Loss on chromosome 16 occurred in 34 of 73 HCCs. Of 11 HCC cell lines, 2 had low, 7 intermediate, and 2 had high WWOX mRNA. Of 51 primary tumors, 23 had low WWOX mRNA. Forced expression of WWOX in SNU387 cells decreased FGF2-mediated proliferation and enhanced apoptosis induced by staurosporine and the JNK inhibitor SP600129. Conversely, knockdown of WWOX in SNU449 cells using shRNA targeting WWOX increased proliferation and resistance to SP600129-induced apoptosis. Conclusions: WWOX induces apoptosis and inhibits human HCC cell growth through a mechanism enhanced by JNK inhibition.
KW - Apoptosis
KW - Hepatocellular carcinoma
KW - JNK
KW - WWOX
UR - http://www.scopus.com/inward/record.url?scp=48449090284&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48449090284&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2008.05.015
DO - 10.1016/j.jhep.2008.05.015
M3 - Article
C2 - 18620777
AN - SCOPUS:48449090284
VL - 49
SP - 373
EP - 383
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 3
ER -