title: The HER2-binding affibody molecule (Z(HER2∶342))₂ increases radiosensitivity in SKBR-3 cells.
abstract: We have previously shown that the HER2-specific affibody molecule (Z(HER2∶342))₂ inhibits proliferation of SKBR-3 cells. Here, we continue to investigate its biological effects in vitro by studying receptor dimerization and clonogenic survival following irradiation. We found that (Z(HER2∶342))₂ sensitizes the HER2-overexpressing cell line SKBR-3 to ionizing radiation. The survival after exposure to (Z(HER2∶342))₂ and 8 Gy (S(8Gy) 0.006) was decreased by a factor four compared to the untreated (S(8Gy) 0.023). The low HER2-expressing cell line MCF-7 was more radiosensitive than SKBR-3 but did not respond to (Z(HER2∶342))₂. Treatment by (Z(HER2∶342))₂ strongly increased the levels of dimerized and phosphorylated HER2 even after 5 minutes of stimulation. The monomeric Z(HER2∶342) does not seem to be able to induce receptor phosphorylation and dimerization or sensitize cells to irradiation.
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Ekerljung
authors.forename: Johan
authors.initials: J
authors.lastname: Lennartsson
authors.forename: Lars
authors.initials: L
authors.lastname: Gedda
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D011836:Radiation Tolerance / Q000187:drug effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C533351:affibody (ZHER2-342)2