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Preclinical modeling of endocrine response and resistance : Focus on aromatase inhibitors by Luciana F. Macedo; Gauri Sabnis; Angela Brodie is a Medicine article available to read on EtoBox.

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The authors developed a breast cancer intratumoral aromatase model system to compare the antitumor efficacy of several aromatase inhibitors (AIs) and antiestrogens (AEs). Although the AI letrozole caused sustained growth inhibition, tumors eventually began to grow, even when treatment was maintained. For the current study, the mechanisms of resistance to letrozole during the course of treatment were investigated. Estrogen receptor alpha (ER-alpha) levels decreased below control levels in letrozole-resistant tumors. The decrease was simultaneous to an increase in phosphorylation of ER-alpha and an unaltered expression of progesterone receptor (PgR). Expression levels of HER-2, activated (phosphorylated) SHC-adaptor protein (p-Shc), growth factor receptor-bound protein 2 (Grb-2), p-Raf, phosphorylated mitogen-activated protein kinase kinase 1/2 (p-Mekl/2), and phosphorylated mitogen-activated protein kinase (p-MAPK) were increased. When cells isolated from letrozole-resistant tumors (LTLTCa cells) were treated with inhibitors of the HER-2 signaling pathway, ER-alpha expression and estradiol-stimulated transactivation was restored. The HER-2 blocker trastuzumab also restored the sensi

Who reads Preclinical modeling of endocrine response and resistance : Focus on aromatase inhibitors?

Author

Luciana F. Macedo; Gauri Sabnis; Angela Brodie

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0008-543X)

Published

2008

Language

EN

Field

Medicine (Health Sciences)