Inducible Expression of RbAp46 Activates c-Jun NH2-terminal Kinase-dependent Apoptosis and Suppresses Progressive Growth of Tumor Xenografts in Nude Mice

Teng Fei Zhang, Shui Qing Yu, Brian W. Loggie, Zhao Yi Wang

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish
Pages (from-to)4621-4627
Number of pages7
JournalAnticancer Research
Volume23
Issue number6 C
StatePublished - Nov 2003

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JNK Mitogen-Activated Protein Kinases
Heterografts
Nude Mice
Apoptosis
Growth
Neoplasms
Proteins
Retinoblastoma-Binding Protein 7
Phosphotransferases
Tetracycline
Tumor Cell Line
Histones
Transplants
Phenotype

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 journalArticle

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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.",
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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.

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