Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of androgen-independent prostate cancer
Autor: | William L. Gerald, Michael M. Shen, Cory Abate-Shen, Hui Gao, Whitney Banach-Petrosky, Xuesong Ouyang |
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Rok vydání: | 2006 |
Předmět: |
Male
Proto-Oncogene Proteins B-raf MAPK/ERK pathway medicine.medical_specialty Context (language use) urologic and male genital diseases Mice Prostate cancer Prostate Internal medicine medicine Animals PTEN Extracellular Signal-Regulated MAP Kinases Protein kinase B Cells Cultured Multidisciplinary biology PTEN Phosphohydrolase Prostatic Neoplasms Biological Sciences medicine.disease Mice Mutant Strains Rats Enzyme Activation Androgen receptor Disease Models Animal Endocrinology medicine.anatomical_structure Receptors Androgen Androgens biology.protein Cancer research Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
Zdroj: | Proceedings of the National Academy of Sciences. 103:14477-14482 |
ISSN: | 1091-6490 0027-8424 |
Popis: | Androgen independence is responsible for most prostate cancer lethality, yet currently there are no effective clinical treatments. We have been investigating the mechanisms underlying androgen-independent prostate cancer in Nkx3.1;Pten mutant mice, which display salient features of the disease, including a requirement for wild-type androgen receptor (AR) signaling. We now demonstrate that the Akt and Erk MAP kinase signaling pathways are activated in androgen-independent lesions of these mice. Forced activation of either Akt or Erk signaling in an androgen-responsive prostate cancer cell line promotes hormone-independent but AR-dependent growth in culture. Although these pathways act additively in culture, they act synergistically in vivo to promote tumorigenicity and androgen independence in the context of the prostate microenvironment. We propose that androgen independence emerges by means of epithelial–stromal competition, in which activation of Akt and Erk promotes AR activity in the prostate epithelium while counteracting antagonistic effects of the stroma. |
Databáze: | OpenAIRE |
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