The goal of this application is to utilize the GH4 cell line to elucidate the cellular processes by which growth factors inhibit pituitary cell proliferation. It is proposed to investigate several aspects of TGF-alpha and TGF-beta growth-inhibitory mechanisms. First, it will be examined whether TGF-alpha or TGF-beta blocks specific states of the cell cycle. Then it will be examined whether TGF-alpha or TGF-beta inhibits cell proliferation by preventing the actions of defined growth-stimulatory factors, elevating free cytosolic calcium, or enhancing cell-substratum adhesion.
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