| Autor: |
Jer-Tsong Hsieh, Ching-Ping Tseng, Chien-Ling Huang, Szu-Wei Tu, Gina Hernandez, Jian Zhoul |
| Rok vydání: |
2023 |
| DOI: |
10.1158/0008-5472.c.6495935.v1 |
| Popis: |
Prostate cancer is initially responsive to androgen ablation, but prostate cancer tumors invariably progress to an androgen-independent state that is ultimately lethal. The onset of the androgen-independent prostate cancer is often associated with up-regulation of the androgen receptor that can cause antagonists to exhibit agonistic activity, which could lead to the failure of androgen ablation therapy. We describe a unique protein—DOC-2/DAB2 (differentially expressed in ovarian cancer-2/disabled 2)—that antagonizes androgen receptor–mediated cell growth in prostate cancer cells via interaction with c-Src protein. This interaction causes inactivation of Erk and Akt proteins critical for proliferation and survival of prostate cancer cells. However, DOC-2/DAB2 does not change the capacity of androgen receptor to regulate the transcription of androgen-responsive reporter genes, indicating that DOC-2/DAB2 selectively inhibits androgen receptor–mediated cell growth in androgen-independent prostate cancer by disrupting the androgen receptor/c-Src complex. In normal prostatic epithelia, DOC-2/DAB2 protein levels are more abundant than androgen receptor protein levels and reduced endogenous DOC-2/DAB2 protein levels in these cells by DOC-2/DAB2 RNA interference result in enhancing androgen receptor–mediated cell growth. We conclude that DOC-2/DAB2 can modulate androgen receptor–mediated cell growth in both normal and malignant prostatic epithelial cells and the outcome of this study could evolve into a new therapeutic strategy of prostate cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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