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- W3044665618 abstract "1288 Acquired resistance to tamoxifen (Tam) in breast cancer patients is a serious therapeutic problem. We have previously reported that Protein Kinase C-delta (PKC-δ) plays a major role in estrogen (E2)-mediated cell proliferation. To determine if PKC-δ is one of the major alternate signaling pathways that supports cell growth in the presence of tamoxifen, we determined the levels of PKC isoforms in four different models of antiestrogen resistant cells. Three out of four antiestrogen resistance cell lines (Tam/MCF-7, ICI/MCF-7 and HER-2/MCF-7) expressed significantly high levels of both total and activated PKC-δ levels compared to sensitive cells. Estrogen receptor alpha (ER) content and function are maintained in all the antiestrogen resistant cell lines. Overexpressing active PKC-δ in tamoxifen-sensitive MCF-7 cells (PKC-δ/MCF-7) led to tamoxifen resistance both in vitro and in vivo. Inhibition of PKC-δ by rottlerin (a relatively specific inhibitor of PKC-δ) significantly inhibited estrogen- and tamoxifen-induced growth in all antiestrogen resistant cell lines. PKC-δ levels are significantly higher in Tam-resistant tumors compared to Tam-sensitive tumors in xenograft model (P" @default.
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- W3044665618 date "2005-05-01" @default.
- W3044665618 modified "2023-09-27" @default.
- W3044665618 title "Overexpression of PKC-delta in mammary cells leads to anti-estrogen resistance: A new model for anti-estrogen resistance" @default.
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