LZTS1 downregulation confers paclitaxel resistance and is associated with worse prognosis in breast cancer
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Francesca Lovat1, Hideshi Ishii2, Monica Schiappacassi3, Matteo Fassan1,4, Mattia Barbareschi5, Enzo Galligioni5, Pierluigi Gasparini1, Gustavo Baldassarre3, Carlo M. Croce1 and Andrea Vecchione1,6
1 Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, Ohio, USA
2 Department of Frontier Science for Cancer and Chemotherapy Osaka University, Japan.
3 Division of Experimental Oncology 2, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
4 ARC-NET Research Centre, University and Hospital Trust of Verona, Verona, Italy
5 Departments of Pathology and Medical Oncology, Ospedale Santa Chiara, Trento, Italy
6 University of Rome “La Sapienza”, Department of Clinical and Molecular Medicine, Ospedale Santo Andrea, Rome, Italy
Andrea Vecchione, email:
Keywords: Lzts1/Fez1; breast cancer; taxanes
Received: November 26, 2013 Accepted: December 14, 2013 Published: December 14, 2013
The Leucine Zipper Tumor Suppressor 1 (LZTS1) is a tumor suppressor gene, located at chromosome 8p22, which is frequently altered in human cancer. In normal tissue, its ubiquitous expression regulates cell mitosis by the stabilization of microtubule networks. LZTS1-deficient mouse embryonic fibroblasts have been shown to have an accelerated mitotic progression, and a higher resistance to taxanes, microtubule-stabilizing drugs.
We investigate the role of Lzts1 in paclitaxel-resistance in breast cancer cells. Downregulation of Lzts1 expression significantly decreases sensitivity to paclitaxel in vitro. We further analyzed Lzts1 expression by immunohistochemistry in 270 primary breast cancer samples and 16 normal breast specimens.
Lzts1 was significantly downregulated in breast cancer samples and its deregulation was associated with a higher incidence of tumor recurrence, and to a worse overall survival. Moreover, Lzts1-negative tumors were associated with unfavorable outcome after taxanes-based therapy.
Thus our data suggest that Lzts1 deregulation is involved in breast cancer and its immunohistochemical evaluation may serve as a prognostic factor for breast cancer therapy
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