Abstract
Background: The retinoblastoma (Rb) suppressor-associated protein 46 (RbAp46) is a member of the WD-repeat protein family and a component of histone modifying and remodeling complexes. Previously, we demonstrated that RbAp46 inhibits cell growth and suppresses the transformed phenotypes of tumor cell lines. Materials and Methods: We established a tetracycline-inducible RbAp46 expression system in Saos-2 cells to test the effects of RbAp46 induction on cell growth in vitro and on tumor formation in vivo. Results: We found that inducible expression of RbAp46 activated the c-Jun N-terminal kinase (JNK) signaling pathway and triggered apoptosis in Saos-2 cells. A dominant-negative mutant of JNK1, which can inhibit RbAp46-induced JNK activity, blocked RbAp46-mediated apoptosis. We also found that the induction of RbAp46 expression strongly suppressed the formation of tumors grafted in nude mice and drastically reduced growth of established tumor xenografts. Conclusion: These results revealed a novel proapoptotic activity for RbAp46 via the JNK pathway and demonstrated that induction of RbAp46 expression inhibits progressive growth of tumor grafts in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 4621-4627 |
| Number of pages | 7 |
| Journal | Anticancer Research |
| Volume | 23 |
| Issue number | 6 C |
| State | Published - Nov 2003 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Cancer Research
- Oncology
Cite this
Inducible Expression of RbAp46 Activates c-Jun NH2-terminal Kinase-dependent Apoptosis and Suppresses Progressive Growth of Tumor Xenografts in Nude Mice. / Zhang, Teng Fei; Yu, Shui Qing; Loggie, Brian W.; Wang, Zhao Yi.
In: Anticancer Research, Vol. 23, No. 6 C, 11.2003, p. 4621-4627.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inducible Expression of RbAp46 Activates c-Jun NH2-terminal Kinase-dependent Apoptosis and Suppresses Progressive Growth of Tumor Xenografts in Nude Mice
AU - Zhang, Teng Fei
AU - Yu, Shui Qing
AU - Loggie, Brian W.
AU - Wang, Zhao Yi
PY - 2003/11
Y1 - 2003/11
N2 - Background: The retinoblastoma (Rb) suppressor-associated protein 46 (RbAp46) is a member of the WD-repeat protein family and a component of histone modifying and remodeling complexes. Previously, we demonstrated that RbAp46 inhibits cell growth and suppresses the transformed phenotypes of tumor cell lines. Materials and Methods: We established a tetracycline-inducible RbAp46 expression system in Saos-2 cells to test the effects of RbAp46 induction on cell growth in vitro and on tumor formation in vivo. Results: We found that inducible expression of RbAp46 activated the c-Jun N-terminal kinase (JNK) signaling pathway and triggered apoptosis in Saos-2 cells. A dominant-negative mutant of JNK1, which can inhibit RbAp46-induced JNK activity, blocked RbAp46-mediated apoptosis. We also found that the induction of RbAp46 expression strongly suppressed the formation of tumors grafted in nude mice and drastically reduced growth of established tumor xenografts. Conclusion: These results revealed a novel proapoptotic activity for RbAp46 via the JNK pathway and demonstrated that induction of RbAp46 expression inhibits progressive growth of tumor grafts in vivo.
AB - Background: The retinoblastoma (Rb) suppressor-associated protein 46 (RbAp46) is a member of the WD-repeat protein family and a component of histone modifying and remodeling complexes. Previously, we demonstrated that RbAp46 inhibits cell growth and suppresses the transformed phenotypes of tumor cell lines. Materials and Methods: We established a tetracycline-inducible RbAp46 expression system in Saos-2 cells to test the effects of RbAp46 induction on cell growth in vitro and on tumor formation in vivo. Results: We found that inducible expression of RbAp46 activated the c-Jun N-terminal kinase (JNK) signaling pathway and triggered apoptosis in Saos-2 cells. A dominant-negative mutant of JNK1, which can inhibit RbAp46-induced JNK activity, blocked RbAp46-mediated apoptosis. We also found that the induction of RbAp46 expression strongly suppressed the formation of tumors grafted in nude mice and drastically reduced growth of established tumor xenografts. Conclusion: These results revealed a novel proapoptotic activity for RbAp46 via the JNK pathway and demonstrated that induction of RbAp46 expression inhibits progressive growth of tumor grafts in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0842311697&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0842311697&partnerID=8YFLogxK
M3 - Article
VL - 23
SP - 4621
EP - 4627
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 6 C
ER -