@entity545 is a @entity81 of the tunica albuginea, characterized by development of a plaque consisting primarily of collagen. It has been suggested that @entity130 to the erect penis is the inciting event. More recent research has focused on the cellular events leading to the dysregulated wound healing and plaque formation. Previous work has shown chromosomal aneusomies and this combined with an increased S-phase in plaque derived cell cultures suggests a perturbation in the cell cycle in this condition. The @entity876 protein has been shown to be an important cell cycle regulator and pro-apoptotic factor. Aberrant @entity876 function leading to cell immortalization and proliferation has been implicated in several @entity1 @entity5 . We hypothesized that abnormal @entity876 function may explain the high proliferative ability of fibroblasts derived from @entity545 . This study was undertaken to study the presence and function of @entity876 and its downstream elements ( @entity3544 , @entity7465 ) in @entity545 cell cultures. Plaque-derived fibroblasts have been established in culture and characterized. These cells and control neonatal foreskin fibroblasts were subjected to 5 Gy of gamma radiation to induce DNA damage. After fixation, antibodies to @entity876 and its transcriptional elements were used to stain irradiated and non-irradiated cells and levels of @entity876 , @entity3544 and @entity7465 were quantified using combined immunofluorescence and flow cytometry. Non-irradiated plaque fibroblasts demonstrated the presence of @entity876 , @entity3544 and @entity7465 at baseline. In control foreskin fibroblasts no @entity876 or @entity7465 were detectable at baseline. In irradiated foreskin-derived cells significant changes in all elements were demonstrated indicating a fully functional @entity876 pathway and cell cycle checkpoint system in these cells. In contrast, plaque-derived cells showed no such alterations in levels of cell cycle regulators following irradiation. This is highly suggestive of an aberration of the @entity876 pathway in plaque-derived fibroblasts. Peyronie's plaque-derived fibroblasts demonstrated stabilization and defunctionalization of @entity876 protein combined with appropriate responses of its transcriptional elements. These findings may explain the high cell proliferation rates in these cells and suggests a role for perturbation of the @entity876 pathway in the pathogenesis of @entity545 .

Perturbation of cell cycle regulators in XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity5 :: ('MESH:D009369', 'Disease') :: ['malignancies'] @entity545 :: ('MESH:D010411', 'Disease') :: ["Peyronie's plaques", "Peyronie's disease"] @entity7465 :: ('4193', 'Gene') :: ['mdm-2'] @entity3544 :: ('644914', 'Gene') :: ['p21'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity81 :: ('MESH:D005350', 'Disease') :: ['fibromatosis'] @entity130 :: ('MESH:D014947', 'Disease') :: ['trauma']
@entity545 :: (MESH:D010411,Disease) :: ['Peyronie's disease']
