Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 970-977 |
| Number of pages | 8 |
| Journal | Oncotarget |
| Volume | 5 |
| Issue number | 4 |
| Publication status | Published - 2014 |
Fingerprint
Keywords
- Breast cancer
- Lzts1/Fez1
- Taxanes
ASJC Scopus subject areas
- Oncology
- Medicine(all)
Cite this
LZTS1 downregulation confers paclitaxel resistance and is associated with worse prognosis in breast cancer. / Lovat, Francesca; Ishii, Hideshi; Schiappacassi, Monica; Fassan, Matteo; Barbareschi, Mattia; Galligioni, Enzo; Gasparini, Pierluigi; Baldassarre, Gustavo; Croce, Carlo M.; Vecchione, Andrea.
In: Oncotarget, Vol. 5, No. 4, 2014, p. 970-977.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - LZTS1 downregulation confers paclitaxel resistance and is associated with worse prognosis in breast cancer
AU - Lovat, Francesca
AU - Ishii, Hideshi
AU - Schiappacassi, Monica
AU - Fassan, Matteo
AU - Barbareschi, Mattia
AU - Galligioni, Enzo
AU - Gasparini, Pierluigi
AU - Baldassarre, Gustavo
AU - Croce, Carlo M.
AU - Vecchione, Andrea
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Lzts1/Fez1
KW - Taxanes
UR - http://www.scopus.com/inward/record.url?scp=84897469173&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897469173&partnerID=8YFLogxK
M3 - Article
C2 - 24448468
AN - SCOPUS:84897469173
VL - 5
SP - 970
EP - 977
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 4
ER -