Premium
Differential modulation of p‐4EBP1, p‐ERK and cyclin D1 by amuvatinib/erlotinib treatment in prostate cancer cells (1055.4)
Author(s) -
Canatsey Ryan,
Cai Wesley,
Mastrandrea Nicholas,
Gard Jaime,
Nagle Ray,
Monks Terrence,
Lau Serrine
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1055.4
Subject(s) - erlotinib , cyclin d1 , cancer research , lncap , du145 , epidermal growth factor receptor , medicine , pharmacology , cancer , chemistry , prostate cancer , cell cycle
Cyclin D1 is a key regulator of cell cycle progression and a therapeutic endpoint for cancer treatment. The human prostate cancer cell lines, LNCaP (PTEN ‐ ) and DU145 (PTEN + ), were used to examine the differential regulation of cyclin D1 as a determinant of drug sensitivity to amuvatinib, a receptor tyrosine kinase inhibitor, and erlotinib, an epidermal growth factor inhibitor. 1D and 2D Western blot analysis revealed that combination drug treatment of LNCaP cells caused a decrease in 4EBP1 pSer65, pThr70, and pThr37/46, with concomitant decreases in cyclin D1 levels. Such combination treatment, however, did not modulate pERK status. Moreover, single drug treatment with amuvatinib, but not erlotinib, decreased p‐4EBP1 and cyclin D1 levels. In DU‐145 cells, combination drug treatment had no effect on p‐4EBP1 status, but decreased p‐ERK and cyclin D1 levels. Additionally, single drug treatment with erlotinib, but not amuvatinib, caused a loss of p‐ERK and cyclin D1. The data reveal the differential modulation of cyclin D1, and its upstream regulators, in prostate cancer cell lines by amuvatinib and erlotinib. Such differential responses likely contribute to specific anti‐tumor agent efficacy. An appreciation of factors that determine the cell‐dependent modulation of cyclin D1 will assist in the selection of appropriate biomarkers for directing patient‐targeted therapy. Grant Funding Source : Supported by Ventana/Roche, P30 ES006694