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Breast Cancer Research and Treatment

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01.06.2015 | Preclinical study

CD44 expression contributes to trastuzumab resistance in HER2-positive breast cancer cells

verfasst von: Delphine R. Boulbes, Gaurav B. Chauhan, Quanri Jin, Chandra Bartholomeusz, Francisco J. Esteva

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2015

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Abstract

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. CD44, a putative breast cancer stem cell (CSC) marker, is overexpressed in trastuzumab-resistant breast cancer cells. While CSC-related genes may play a role in the development of trastuzumab resistance, conflicting results have been published about CSC response to trastuzumab. We hypothesized that CD44 contributes to trastuzumab resistance independently of its role as a CSC marker. We used trastuzumab-sensitive breast cancer cell lines and their trastuzumab-resistant isogenic counterparts to evaluate the role of CD44 in response to trastuzumab. miRNA and mRNA expression were analyzed using microarray chips. A gene set enrichment analysis was created and matched with response to trastuzumab in cells and patient samples. The proportions of CSC in trastuzumab-resistant cells were similar to or lower than in the trastuzumab-sensitive cells. However, CD44 expression levels were significantly higher in both trastuzumab-resistant cell lines and its knockdown led to an increased response to trastuzumab. The invasiveness and anchorage-independent growth of trastuzumab-resistant cells were higher and blocked by downregulation of CD44. Results also showed that CD44-related resistance to trastuzumab is regulated by miRNAs. We identified a CD44-related gene expression profile that correlated with response to trastuzumab in cell lines and breast cancer patients. CD44 mediates trastuzumab resistance in HER2-positive breast cancer cells independently of its role as a CSC marker and that this role of CD44 is partly regulated by miRNA.

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Titel: CD44 expression contributes to trastuzumab resistance in HER2-positive breast cancer cells
verfasst von: Delphine R. Boulbes
Gaurav B. Chauhan
Quanri Jin
Chandra Bartholomeusz
Francisco J. Esteva
Publikationsdatum: 01.06.2015
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2015
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3414-3

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25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

CD44 expression contributes to trastuzumab resistance in HER2-positive breast cancer cells

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