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PROSTATIC DISEASES - PART 3

Tăng trưởng yếu tố như yếu tố tăng trưởng biểu bì (EGF) hành động như các phân tử tín hiệu trên các thụ thể cụ thể trên màng tế bào. Liên kết của các EGF kết quả thụ thể của nó trong một số thay đổi trong tế bào lên đến đỉnh cao trong sự tăng trưởng và phân chia của tế bào | MOLECULAR MECHANISMS UNDERLYING PROSTATE GROWTH Figure 22 Growth factors such as epidermal growth factor EGF act as signal molecules on specific receptors on the cell membrane. The binding of EGF to its receptor results in a number of intracellular changes that culminate in cell growth and division Figure 23 Factors such as the fos and jun proteins encoded by the c-fos and c-jun proto-oncogenes are intimately concerned with growth regulation. The fos and jun proteins bind as heterodimers to specific recognition sites on the genome characterized by the nucleotide sequence TGACTCA which is adjacent to the androgen response element 27 AN ATLAS OF PROSTATIC DISEASES closely associated with the androgen response area on the genome. This association allows cross-talk between the two signalling pathways Figure 24 . Other pathways involved in prostate growth include the endothelin axis Figure 25 . Endothelin-1 ET-1 induces cell proliferation by production of kinases involved in cell cycle regulation including mitogen-activated protein kinase MAPK and inhibition of cell death apoptosis . Figure 24 The proximity of the recognition sites to which the fos and jun proteins bind to the androgen response element allows cross-talk between the two signalling pathways. It has been suggested that the association of DHT and the AR results in opening up of the DNA strands so as to provide better access for the transcription factors thereby facilitating a more effective binding of the fos-jun heterodimer complex 28 MOLECULAR MECHANISMS UNDERLYING PROSTATE GROWTH Figure 25 Stimulating the ETa receptor with ET-1 triggers a signal transduction pathway that acts on a G protein Gq causing hydrolysis of phospholipase-C PLC-P and forming diacylglycerol DG and inositol 1 4 5 triphosphate nsP3 . Intracellular calcium is mobilized from cytoplasmic stores by InsP3 and acting with DG activates protein kinase C PKC and subsequently the Raf MEK MAPK pathway. Activated MAPK mitogen-activated protein .