We propose that this elevated content of raft-specific lipids consequently leads to alterations of DRM density

Here, we investigate the presence of Butenafine hydrochloride a1A-AR in caveolae of DU145 cells, an androgen-independent PCa cell line derived from brain metastasis. We analyze the consequence of a1A-AR LOUREIRIN-B stimulation by PHE on the receptor and cav-1 membrane distribution as well as its effect on the lipid composition of membrane raft fractions purified from DU145 cells. Furthermore, we describe the effect of PHE in the apoptosis resistance of these cells through activation of ERK and our results strongly imply the involvement of caveolae in this signalling pathway. Finally, by immunohistofluorescence and RT-PCR, we observe a positive correlation of a1A-AR and cav-1 expression and advanced stage PCa. The presence of a1A-AR-rich caveolae could therefore contribute to the generalized apoptosis resistance characterizing androgen-independent prostatic tissue. Various locally produced and circulating factors maintain prostate cancer growth by acting through cellular receptors. Increasing evidence supports the involvement of GPCR in neoplastic transformation of the prostate. Moreover, cancerous prostate expresses increased levels of GPCR and their ligands suggesting that GPCR signalling may always be “switched on” therefore contributing to the initiation and progression of the disease. A growing number of recent data has shown the involvement of a1A-AR in human prostate pathology. Further lines of evidence have demonstrated that a1A-AR and its effector proteins are differentially distributed in surface caveolae of cardiac cells. Caveolae and cav-1 have been described to play prominent roles in various human disease phenotypes including cancer. Interestingly, the expression of cav-1 has been identified to be closely associated with PCa malignant progression and highly expressed in androgen-independent cells. Despite the above findings, the precise surface localization of the a1A-AR in androgen-independent PCa epithelial cells and its functional role in the proliferation and survival of these cells remain unknown. The present study is the first to demonstrate the localization of a1A-AR in caveolae of the androgen-independent PCa epithelial cells DU145. Our results from the exploration of the lipid-protein contents of purified DRM from these cells were particularly revealing. Noticeably, we provide evidence of significant increase in DRM lipids upon agonist stimulation of the a1A-AR.

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