Albert, Veruschka and Piendl, Gerhard and Yousseff, Dali and Lammert, Hedwig and Hummel, Michael and Ortmann, Olaf and Jagla, Wolfgang and Gaumann, Andreas and Wege, Anja K. and Brockhoff, Gero (2022) Protein kinase C targeting of luminal (T-47D), luminal/HER2-positive (BT474), and triple negative (HCC1806) breast cancer cells in-vitro with AEB071 (Sotrastaurin) is efficient but mediated by subtype specific molecular effects. ARCHIVES OF GYNECOLOGY AND OBSTETRICS, 306 (4). pp. 1197-1210. ISSN 0932-0067, 1432-0711
Full text not available from this repository. (Request a copy)Abstract
Purpose Protein kinase C (PKC) plays a pivotal role in malignant cell proliferation, apoptosis, invasiveness and migration. However, its exploitation as therapeutic target in breast cancer has been merely explored. Here were evaluated the AEB071 (Sotrastaurin (TM)) treatment efficiency of breast cancer cell lines derived from estrogen receptor positive (T-47D), estrogen/HER2 receptor positive (BT474), and triple negative (HCC1806) breast cancer cells under 2D (monolayer) and 3D (multicellular tumor spheroids) culture conditions. Additionally, spheroid cocultures of BC and N1 fibroblasts were analyzed. Methods We quantitatively assessed the proliferation capacity of breast cancer cells and fibroblasts as a function of AEB071 treatment using flow cytometry. The activities of PKC isoforms, substrates, and key molecules of the PKC signaling known to be involved in the regulation of tumor cell proliferation and cellular survival were additionally evaluated. Moreover, a multigene expression analysis (PanCancer Pathways assay) using the nanoString (TM) technology was applied. Results All breast cancer cell lines subjected to this study were sensitive to AEB071 treatment, whereby cell proliferation in 2D culture was considerably (BT474) or moderately (HCC1806) retarded in G0/G1 or in G2/M phase (T-47D) of the cell cycle. Regardless of the breast cancer subtype the efficiency of AEB071 treatment was significantly lower in the presence of N1 fibroblast cells. Subtype specific driver molecules, namely IL19, c-myb, and NGFR were mostly affected by the AEB071 treatment. Conclusion A combined targeting of PKC and a subtype specific driver molecule might complement specified breast cancer treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INHIBITOR AEB071; ALPHA EXPRESSION; PKC; PROMOTES; MODEL; Protein kinase C; AEB071; Sotrastaurin; Breast cancer |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Feb 2024 15:11 |
| Last Modified: | 08 Feb 2024 15:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57368 |
Actions (login required)
 |
View Item |
