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Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines.
Mol Cancer Res. 2006 Apr; 4(4):235-46.MC

Abstract

Transforming growth factor-beta superfamily has been implicated in tumorigenesis. We have recently shown that Nodal, a member of transforming growth factor-beta superfamily, and its receptor, activin receptor-like kinase 7 (ALK7), inhibit proliferation and induce apoptosis in human epithelial ovarian cancer cell lines. In this study, we further investigated the cellular mechanisms underlying the apoptotic action of ALK7 using an immortalized ovarian surface epithelial cell line, IOSE397, and an epithelial ovarian cancer cell line, OV2008. Infection of these cells with an adenoviral construct carrying constitutively active ALK7 (Ad-ALK7-ca) potently induced cell death; all cells died after 3 and 5 days of Ad-ALK7-ca infection in IOSE397 and OV2008 cells, respectively. ALK7-ca induced the expression of proapoptotic factor Bax but suppressed the expression of antiapoptotic factors Bcl-2, Bcl-XL, and Xiap. Silencing of Bax by small interfering RNA in IOSE397 cells significantly reduced ALK7-ca-induced apoptosis as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay but partially blocked ALK7-ca-induced caspase-3 activation and did not affect the down-regulation of Xiap by ALK7-ca. Dominant-negative Smad2, Smad3, and Smad4 blocked ALK7-ca-regulated Xiap and Bax expression and caspase-3 activation. Thus, ALK7-induced apoptosis is at least in part through two Smad-dependent pathways, Bax/Bcl-2 and Xiap.

Authors+Show Affiliations

Department of Biology, York University, 4700 Keel Street, Toronto, Ontario, Canada M3J 1P3.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16603637

Citation

Xu, Guoxiong, et al. "Activin Receptor-like Kinase 7 Induces Apoptosis Through Up-regulation of Bax and Down-regulation of Xiap in Normal and Malignant Ovarian Epithelial Cell Lines." Molecular Cancer Research : MCR, vol. 4, no. 4, 2006, pp. 235-46.
Xu G, Zhou H, Wang Q, et al. Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines. Mol Cancer Res. 2006;4(4):235-46.
Xu, G., Zhou, H., Wang, Q., Auersperg, N., & Peng, C. (2006). Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines. Molecular Cancer Research : MCR, 4(4), 235-46.
Xu G, et al. Activin Receptor-like Kinase 7 Induces Apoptosis Through Up-regulation of Bax and Down-regulation of Xiap in Normal and Malignant Ovarian Epithelial Cell Lines. Mol Cancer Res. 2006;4(4):235-46. PubMed PMID: 16603637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines. AU - Xu,Guoxiong, AU - Zhou,Hong, AU - Wang,Qinghua, AU - Auersperg,Nelly, AU - Peng,Chun, PY - 2006/4/11/pubmed PY - 2006/5/19/medline PY - 2006/4/11/entrez SP - 235 EP - 46 JF - Molecular cancer research : MCR JO - Mol. Cancer Res. VL - 4 IS - 4 N2 - Transforming growth factor-beta superfamily has been implicated in tumorigenesis. We have recently shown that Nodal, a member of transforming growth factor-beta superfamily, and its receptor, activin receptor-like kinase 7 (ALK7), inhibit proliferation and induce apoptosis in human epithelial ovarian cancer cell lines. In this study, we further investigated the cellular mechanisms underlying the apoptotic action of ALK7 using an immortalized ovarian surface epithelial cell line, IOSE397, and an epithelial ovarian cancer cell line, OV2008. Infection of these cells with an adenoviral construct carrying constitutively active ALK7 (Ad-ALK7-ca) potently induced cell death; all cells died after 3 and 5 days of Ad-ALK7-ca infection in IOSE397 and OV2008 cells, respectively. ALK7-ca induced the expression of proapoptotic factor Bax but suppressed the expression of antiapoptotic factors Bcl-2, Bcl-XL, and Xiap. Silencing of Bax by small interfering RNA in IOSE397 cells significantly reduced ALK7-ca-induced apoptosis as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay but partially blocked ALK7-ca-induced caspase-3 activation and did not affect the down-regulation of Xiap by ALK7-ca. Dominant-negative Smad2, Smad3, and Smad4 blocked ALK7-ca-regulated Xiap and Bax expression and caspase-3 activation. Thus, ALK7-induced apoptosis is at least in part through two Smad-dependent pathways, Bax/Bcl-2 and Xiap. SN - 1541-7786 UR - https://www.unboundmedicine.com/medline/citation/16603637/Activin_receptor_like_kinase_7_induces_apoptosis_through_up_regulation_of_Bax_and_down_regulation_of_Xiap_in_normal_and_malignant_ovarian_epithelial_cell_lines_ L2 - http://mcr.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16603637 DB - PRIME DP - Unbound Medicine ER -