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

URN zum Zitieren dieses Dokuments:

urn:nbn:de:bvb:355-epub-519519 Copy

DOI zum Zitieren dieses Dokuments:

10.5283/epub.51951 Copy

Albert, Veruschka ; Piendl, Gerhard ; Yousseff, Dali ; Lammert, Hedwig ; Hummel, Michael ; Ortmann, Olaf ; Jagla, Wolfgang ; Gaumann, Andreas ; Wege, Anja K. ; Brockhoff, Gero

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Lizenz: Creative Commons Namensnennung 4.0 International PDF - Veröffentlichte Version (2MB)

Veröffentlichungsdatum dieses Volltextes: 22 Mrz 2022 05:45

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Diese Publikation ist Teil des DEAL-Vertrags mit Springer.

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Details

Dokumentenart:	Artikel
Open Access Art:	DEAL (Springer)
Titel eines Journals oder einer Zeitschrift:	Archives of Gynecology and Obstetrics
Verlag:	SPRINGER HEIDELBERG
Ort der Veröffentlichung:	HEIDELBERG
Datum:	17 März 2022
Institutionen:	Medizin > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde)
Identifikationsnummer:	Wert Typ 10.1007/s00404-022-06434-2 DOI
Stichwörter / Keywords:	INHIBITOR AEB071; ALPHA EXPRESSION; PKC; PROMOTES; MODEL; Protein kinase C; AEB071; Sotrastaurin; Breast cancer
Dewey-Dezimal-Klassifikation:	600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
Status:	Veröffentlicht
Begutachtet:	Ja, diese Version wurde begutachtet
An der Universität Regensburg entstanden:	Zum Teil
Dokumenten-ID:	51951

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Zusammenfassung

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 ...

Zusammenfassung

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.

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Metadaten zuletzt geändert: 26 Jan 2023 15:23

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