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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo.
Mol. Oncol. 9, 282-294 (2015)
The human epidermal growth factor receptor 2 (HER2) and the protein tyrosine kinase 6 (PTK6) are often co- and over-expressed in invasive breast cancers. At early diagnosis, only distinct groups, such as HER2-or hormone receptor-positive benefit from a targeted therapy. However, a part of these tumours develops resistance within a year of administration of the drug but the majority of the patients depends on general therapies with severe side effects. A PTK6-directed approach does not yet exist. In our present study, we successfully demonstrate, in vitro and in vivo, a significantly additive reduction of tumourigenesis of breast cancer cells simultaneously depleted of both HER2 and PTK6. In comparison with single RNAi approaches, the combined RNAi (co-RNAi) led to a stronger reduced phosphorylation of tumour-promoting proteins. Moreover, the co-RNAi additively decreased cell migration as well as two and three dimensional cell proliferation in vitro. The in vivo experiments showed an additive reduction (p < 0.00001) in the growth of xenografts due to the co-RNAi compared with HER2 or PTK6 RNAi alone. Interestingly, the complexes of HER2 or PTK6 with tumour-relevant interaction partners, such as HER3 or the insulin-like growth factor receptor 1 (IGF-1R), respectively, were also reduced in xenografts although their protein expression levels were not affected following the co-RNAi of HER2 and PTK6. Our present study reveals the potential of using combined HER2- and PTK6- knockdown as a powerful strategy for the treatment of breast cancers. Therefore, the combined inhibition of these proteins may represent an attractive tool for efficient therapy of breast cancers.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Brk ; Combined ; Erbb2 ; Pla ; Proximity Ligation Assay ; Rna Interference; Mammary Epithelial-cells; Mediated Down-regulation; Brk Tyrosine Kinase; Tumor Kinase; Growth-factor; Receptor; Expression; Angiogenesis; Trastuzumab; Invasion
ISSN (print) / ISBN
1574-7891
e-ISSN
1878-0261
Zeitschrift
Molecular Oncology
Quellenangaben
Band: 9,
Heft: 1,
Seiten: 282-294
Verlag
Elsevier
Verlagsort
Amsterdam [u.a.]
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed