Abstract
The molecular mechanisms underlying prostate development can provide clues for prostate cancer research. It has been demonstrated that MEK/ERK signaling downstream of androgen-targeted FGF10 signaling directly induces prostatic branching during development, while Rho/Rho-kinase can regulate prostate cell proliferation. MEK/ERK and Rho/Rho kinase regulate myosin light chain kinase (MLCK), and MLCK regulates myosin light chain phosphorylation (MLC-P), which is critical for cell fate, including cell proliferation, differentiation, and apoptosis. However, the roles and crosstalk of the MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis have not been examined. In the present study, we used numerical and image analysis to characterize lobe-specific rat prostatic branching during postnatal organ culture and investigated the roles of FGF10-MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis. Prostates exhibited distinctive lobe-specific growth and branching patterns in the ventral (VP) and lateral (LP) lobes, while exogenous FGF10 treatment shifted LP branching towards a VP branching pattern. Treatment with inhibitors of MEK1/2, Rho, Rho kinase, or MLCK significantly inhibited VP growth and blocked branching morphogenesis, further supporting critical roles for MEK/ERK and Rho/Rho kinase signaling pathways in prostatic growth and branching during development. We propose that MLCK-regulated MLC-P may be a central downstream target of both signaling pathways in regulating prostate morphogenesis.
Highlights
Developmental biology contributes greatly to the understanding of cancer biology.Accumulating evidence indicates that cancer contains many features of development gone awry, with several developmental genes frequently reactivated in tumor tissues [1,2].knowledge of the molecular mechanisms underlying organ development is essential for gaining novel insights into cancer growth, its progression, and the development of therapeutical intervention strategies.Prostate development is dependent on androgens and mesenchymal/epithelial interactions [3,4,5,6]
Since the present results using image and numerical morphometry showed that Since the present results using image and numerical morphometry showed that blocking FGF10 downstream signaling using a MEK1 inhibitor reduced VP growth and blocking FGF10 downstream signaling using a MEK1 inhibitor reduced VP growth and branching morphogenesis and shifted the branching pattern towards a LP phenotype, we branching morphogenesis and shifted the branching pattern towards a LP phenotype, we examined the effects of exogenous FGF10 on LP morphogenesis
These results suggest that myosin light chain phosphorylation (MLC-P) is a common target of target of myosin light chain kinase (MLCK), MEK/ERK, Rho signaling, may play a role central role in prostate
Summary
Developmental biology contributes greatly to the understanding of cancer biology.Accumulating evidence indicates that cancer contains many features of development gone awry, with several developmental genes frequently reactivated in tumor tissues [1,2].knowledge of the molecular mechanisms underlying organ development is essential for gaining novel insights into cancer growth, its progression, and the development of therapeutical intervention strategies.Prostate development is dependent on androgens and mesenchymal/epithelial interactions [3,4,5,6]. Developmental biology contributes greatly to the understanding of cancer biology. Accumulating evidence indicates that cancer contains many features of development gone awry, with several developmental genes frequently reactivated in tumor tissues [1,2]. Knowledge of the molecular mechanisms underlying organ development is essential for gaining novel insights into cancer growth, its progression, and the development of therapeutical intervention strategies. Different from the prostate in rodents that consists of anatomically distinct lobes, the human prostate is more compact and composed of three different histological zones.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
