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Falkenberg, N. ; Anastasov, N. ; Höfig, I. ; Bashkueva, K. ; Lindner, K. ; Höfler, H. ; Rosemann, M. ; Aubele, M.

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)
Verlagsversion DOI PMC
Open Access Gold
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
Sprache englisch
Veröffentlichungsjahr 2015
Prepublished im Jahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 1574-7891
e-ISSN 1878-0261
Zeitschrift Molecular Oncology
Quellenangaben Band: 9, Heft: 1, Seiten: 282-294 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pathology (PATH)
Institute of Radiation Biology (ISB)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30202 - Environmental Health
Forschungsfeld(er) Enabling and Novel Technologies
Radiation Sciences
PSP-Element(e) G-500300-001
G-500200-001
PubMed ID 25241146
DOI 10.1016/j.molonc.2014.08.012
WOS ID WOS:000347863700023
Scopus ID 84920367952
Erfassungsdatum 2014-09-24
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