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Open Access Research article

The cyclin-like protein Spy1/RINGO promotes mammary transformation and is elevated in human breast cancer

Mohammad Al Sorkhy1, Rosa-Maria Ferraiuolo2, Espanta Jalili2, Agnes Malysa2, Andreea R Fratiloiu3, Bonnie F Sloane4 and Lisa A Porter2*

Author Affiliations

1 Faculty of Pharmacy, Al Zyatoona Private University, Amman, Jordan

2 Department of Biological Sciences, University of Windsor, ON N9B 3P4 Windsor, Canada

3 Department of Biochemistry, University of Calgary, AB T2N 1 N4 Alberta, Canada

4 Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA

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BMC Cancer 2012, 12:45  doi:10.1186/1471-2407-12-45

Published: 26 January 2012

Abstract

Background

Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis.

Methods

Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation.

Results

We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. Importantly, we show for the first time that enhanced levels of Spy1 protein are found in a large number of human breast cancers and that knockdown of Spy1 impairs breast cancer cell proliferation.

Conclusions

Collectively, this work supports that Spy1 is a unique activator of Cdk1 in breast cancer cells and may represent a valuable drug target and/or a prognostic marker for subsets of breast cancers.