Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer

Breast cancer is a genetically heterogenous disease with subtypes differing in prognosis and chemosensitivity. The basal-like breast cancer (BLBC) molecular subtype is associated with poorer outcomes, but is more responsive to taxane-based chemotherapy. Kinesins are intracellular transport proteins...

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Bibliographic Details
Published in:Breast cancer research and treatment 2012-02, Vol.131 (3), p.849-858
Main Authors: Tan, Min Han, De, Sarmishtha, Bebek, Gurkan, Orloff, Mohammed S., Wesolowski, Robert, Downs-Kelly, Erinn, Budd, G. Thomas, Stark, George R., Eng, Charis
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Adult
Aged
Anthracyclines
Anthracyclines - pharmacology
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Bridged-Ring Compounds - pharmacology
Bridged-Ring Compounds - therapeutic use
Cancer
Cancer research
Cancer therapies
Care and treatment
Cell Line, Tumor
Chemotherapy
Cluster Analysis
Drug resistance
Drug Resistance, Neoplasm - genetics
Female
Gene Expression
Gene Expression Profiling
Genetically modified organisms
Gynecology. Andrology. Obstetrics
HEK293 Cells
Humans
Kinesin
Kinesin - genetics
Kinesin - metabolism
Mammary gland diseases
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Neoplasm Staging
Oncology
Paclitaxel - pharmacology
Preclinical Study
Prognosis
Protein Binding
Proteins
Taxoids - pharmacology
Taxoids - therapeutic use
Tumors
Vincristine - pharmacology
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Summary:Breast cancer is a genetically heterogenous disease with subtypes differing in prognosis and chemosensitivity. The basal-like breast cancer (BLBC) molecular subtype is associated with poorer outcomes, but is more responsive to taxane-based chemotherapy. Kinesins are intracellular transport proteins that interact with microtubules, which are also the mechanistic target for taxanes. We investigated the relationship between taxane resistance in BLBC and kinesins using both expression and functional studies. Kinesin ( KIF ) expression was evaluated in three settings in relation to taxane resistance: (i) the NCI-60 cancer cell lines, (ii) pre-treatment samples from four BLBC patient cohorts receiving neoadjuvant chemotherapy regimens with and without taxanes, and (iii) post-treatment samples from residual breast cancer following neoadjuvant taxane-containing chemotherapy. We used a novel functional approach to gene modification, validation-based insertional mutagenesis, to select kinesin-overexpressing clones of BLBC cells for evaluation of related mechanisms of taxane resistance. In the NCI-60 cell line dataset, overexpression of the kinesin KIFC3 is significantly correlated with resistance to both docetaxel ( P  
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-011-1500-8