Cyclopamine inhibition of human breast cancer cell growth independent of Smoothened (Smo)
| Autor: | Xiaomei Zhang, Ricardo C. Moraes, Meng-Fen Wu, Susan G. Hilsenbeck, Michael T. Lewis, Nikesha Harrington |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
medicine.medical_specialty Cell signaling Cyclopamine Fluorescent Antibody Technique Estrogen receptor Apoptosis Breast Neoplasms Biology Binding Competitive Article Receptors G-Protein-Coupled chemistry.chemical_compound Cell Line Tumor Internal medicine Cell Adhesion medicine Humans Hedgehog Proteins RNA Messenger Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction Veratrum Alkaloids Cancer Flow Cytometry medicine.disease Smoothened Receptor Hedgehog signaling pathway Gene Expression Regulation Neoplastic Cholesterol Endocrinology Receptors Estrogen Oncology chemistry Drug Resistance Neoplasm Cancer research Female Breast disease Growth inhibition Smoothened Signal Transduction |
| Zdroj: | Breast Cancer Research and Treatment. 115:505-521 |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-008-0093-3 |
| Popis: | Altered hedgehog signaling is implicated in the development of approximately 20-25% of all cancers, especially those of soft tissues. Genetic evidence in mice as well as immunolocalization studies in human breast cancer specimens suggest that deregulated hedgehog signaling may contribute to breast cancer development. Indeed, two recent studies demonstrated that anchorage-dependent growth of some human breast cancer cell lines is impaired by cyclopamine, a potent hedgehog signaling antagonist targeting the Smoothened (SMO) protein. However, specificity of cyclopamine at the dosage required for growth inhibition (or =10 microM) remained an open question. In this paper we demonstrate that hedgehog signaling antagonists, including cyclopamine, and a second compound, CUR0199691, can inhibit growth of estrogen receptor (ER)-positive and ER-negative tumorigenic breast cancer cells at elevated doses. However, our results indicate that, for most breast cancer cell lines, growth inhibition by these compounds can be independent of detectable Smo gene expression. Rather, our results suggest that cyclopamine and CUR0199691 have unique secondary molecular targets at the dosages required for growth inhibition that are unrelated to hedgehog signaling. |
| Databáze: | OpenAIRE |
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