Constitutive activation of the Ras/mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells.
نویسندگان
چکیده
Progression of prostate cancer ultimately results in a disease that is refractory to hormone ablation therapy but nevertheless continues to require the androgen receptor. Progression to hormone refractory disease is often correlated with overexpression of growth factors and receptors capable of establishing autocrine and/or paracrine growth-stimulatory loops. Many of these growth factor receptors engage the Ras/mitogen-activated protein (MAP) kinase pathway as part of their signaling activities. This raises the possibility that chronic activation of Ras/MAP kinase signaling could cause or contribute to the progression of prostate cancer. We have demonstrated previously that MAP kinase activation correlates with the progression to advanced hormone refractory disease in patient samples. Here we demonstrate that stable expression of Ras effector-loop mutants that activate the Ras/MAP kinase pathway is sufficient to reduce the androgen requirement of LNCaP prostate cancer cells for growth, prostate-specific antigen expression, and tumorigenicity. We propose that chronic activation of endogenous c-Ras by autocrine and paracrine growth factor stimulation sensitizes the androgen receptor transcriptional complex to subphysiological levels of androgen. This provides a common mechanism for prostate cancer progression driven by diverse agonists.
منابع مشابه
Hypersensitivity in LNCaP Prostate Cancer Cells Kinase Signaling Pathway Promotes Androgen Constitutive Activation of the Ras/Mitogen-activated Protein
Progression of prostate cancer ultimately results in a disease that is refractory to hormone ablation therapy but nevertheless continues to require the androgen receptor. Progression to hormone refractory disease is often correlated with overexpression of growth factors and receptors capable of establishing autocrine and/or paracrine growth-stimulatory loops. Many of these growth factor recepto...
متن کاملInterleukin 6 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells.
Interleukin 6 (IL-6) is a cytokine that regulates not only immune and inflammatory responses but also the growth of some tumors, including prostate carcinomas. IL-6 signals through Janus kinase, signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase and is also able to induce androgen receptor (AR)-mediated gene activation in prostate cancer, which is a...
متن کاملPathway in Prostate Cancer Cell Lines Kinase A Activator on the Mitogen-activated Protein Kinase Action of EGF, Insulin-like Growth Factor I, and a Protein Epidermal Growth Factor (EGF) Receptor Blockade Inhibits the
Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are potent mitogens that regulate proliferation of prostate cancer cells via autocrine and paracrine loops and promote tumor metastasis. They exert their action through binding to the corresponding cell surface receptors that initiate an intracellular phosphorylation cascade, leading to the activation of mitogen-activated pr...
متن کاملEpidermal growth factor (EGF) receptor blockade inhibits the action of EGF, insulin-like growth factor I, and a protein kinase A activator on the mitogen-activated protein kinase pathway in prostate cancer cell lines.
Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are potent mitogens that regulate proliferation of prostate cancer cells via autocrine and paracrine loops and promote tumor metastasis. They exert their action through binding to the corresponding cell surface receptors that initiate an intracellular phosphorylation cascade, leading to the activation of mitogen-activated pr...
متن کاملEffects of Antiproliferative Protein (APP) on Modulation of Cytosolic Protein Phosphorylation of Prostatic Carcinoma Cell Line LNCaP
Antiproliferative protein (APP) isolated from conditioned media of two androgen-independent prostatic carcinoma cell lines, PC3 and Du-145 was shown to inhibit selectively cell proliferation of androgen-dependent prostate cancer cell line LNCaP in a dose dependent manner. This protein was further purified with HPLC using hydrophobic interaction column (phenyl 5PW) and was used to study the modu...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer research
دوره 63 8 شماره
صفحات -
تاریخ انتشار 2003