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- Title:
Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo.
- Document type:
- Journal Article; Research Support, Non-U.S. Gov't
- Author(s):
- Falkenberg, Natalie; Anastasov, Nata?a; Höfig, Ines; Bashkueva, Ksenia; Lindner, Katrin; Höfler, Heinz; Rosemann, Michael; Aubele, Michaela
- Abstract:
- 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.
- Journal title abbreviation:
- Mol Oncol
- Year:
- 2015
- Journal volume:
- 9
- Journal issue:
- 1
- Pages contribution:
- 282-94
- Language:
- eng
- Fulltext / DOI:
- doi:10.1016/j.molonc.2014.08.012
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/25241146
- Print-ISSN:
- 1574-7891
- TUM Institution:
- Institut für Allgemeine Pathologie und Pathologische Anatomie
BibTeX
Occurrences:
- mediaTUM GesamtbestandEinrichtungenSchools TUM School of Medicine and HealthDepartmentsPreclinical MedicineInstitut für Allgemeine Pathologie und Pathologische Anatomie (Dr. Mogler komm.)2015