IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2009;1(1):83-96.

Original Article
Nodal and activin receptor-like kinase 7 induce apoptosis in human breast cancer
cell lines: Role of caspase 3

Yu Zhong, Guoxiong Xu, Gang Ye, Daniel Lee, Joseph Modica-Amore, Chun Peng

Department of Biology, York University, Toronto, Ontario, M3J 1P3, Canada

Received February 20, 2009; accepted February 23, 2009; available online February 27, 2009

Abstract: Nodal is a member of the transforming growth factor β (TGF-β) superfamily that plays critical roles during embyogenesis.
Recently, we have demonstrated that Nodal induces apoptosis and inhibits proliferation in human trophoblast and epithelial ovarian
cancer cells. To further determine the role of Nodal in controlling cellular activities, we examined the action of Nodal and its type I
receptor, activin receptor-like kinase 7 (ALK7), on breast cancer cell lines. Using RT-PCR, we detected Nodal and ALK7 transcripts in
MDA-MB-231 and MCF-7 cells. Overexpression of Nodal or activation of constitutively active ALK7 (ALK7-ca) resulted in a significant
decrease in the number of live cells and a significant increase in the number of dead cells. This effect was observed for both cell lines;
however, Nodal and ALK7-ca had a much stronger effect in MDA-MB-231 cells than in MCF-7 cells. The effect of Nodal was blocked by
dominant negative mutants of ALK7, suggesting that Nodal acts through ALK7 to inhibit cell growth/survival. Nodal and ALK7-ca
inhibited proliferation in both cell lines; however, while Nodal/ALK7-ca induced apoptosis in MDA-MB-231 cells, they only had a minor
effect on MCF-7 cells. While Nodal activated caspase 3 in MDA-MB-231 cells, it had no effect on caspase 3-deficient MCF-7 cells. The
effect of Nodal on apoptosis in MDA-MB-231 cells was blocked by a caspase 3 inhibitor. These findings demonstrate that the Nodal-
ALK7 pathway exerts anti-proliferative and proapoptotic effects in breast cancer cells and suggest that caspase 3 is important for Nodal-
ALK7-induced apoptosis. (IJPPP902006).

Key words: Nodal, ALK7, caspase 3, apoptosis, breast cancer

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Address all correspondence to:
Chun Peng, PhD
Professor, Department of Biology
York University
4700 Keele St., Toronto, Ontario
Tel: 416-7362100 ext 40558
Fax: 416-7365698