XXXX inhibits @entity692 induced mitogenesis and upregulation of @entity3334 , @entity1356 and @entity3840 mRNA in @entity1 @entity0 cell lines.

@entity1 @entity3334 @entity0 @entity1476 @entity5 @entity1421 @entity1356 @entity63886 @entity78 @entity692 @entity1495 @entity460 @entity3840 @entity7999
Microcalcifications containing @entity692 (HA) are often associated with malignant @entity1 breast lesions. Frequently, they are the only mammographic features that indicate the presence of a @entity5 . We previously reported the induction of both mitogenesis and @entity1421 ( @entity1421 ) production and the increased activities of matrix metalloproteinases (MMPs) @entity1476 and @entity1495 in normal @entity1 mammary epithelial cells and @entity0 cell lines, treated with HA. In the present study we attempted to elucidate the mechanism of these biological effects. Firstly, we found that direct cell-crystal contact was required for induction of mitogenesis as the effect was not merely a result of isotopic exchange of @entity460 into the culture medium. Treatment with @entity7999 , a proton pump inhibitor, abrogated HA-induced mitogenesis to control cell levels. These results suggest that phagocytosis and intracellular crystal dissolution is required for HA-induced mitogenesis. We also demonstrated that the increase in @entity1421 , previously reported, is due, at least in part, to HA-induced upregulation of @entity3840 ( @entity3840 ) in Hs578T cells. An accumulation of @entity3334 mRNA was also shown in response to HA stimulation in Hs578T cells. Furthermore, a HA-induced increase in @entity1356 ( @entity1356 ), a potent inducer of @entity3334 gene expression, was demonstrated in Hs578T cells at 2 and 4 h. Treatment with @entity63886 (PC) (a naturally occurring inhibitor of @entity78 crystallisation, which is known to block a number of HA-induced biological effects in other cell types) blocked HA-mediated mitogenesis, as well as, @entity3840 , @entity3334 and @entity1356 induction, at the transcriptional level. These results show that @entity460 HA crystals are capable of exerting significant biological effects on surrounding cells which can be abrogated by PC and emphasise the role of @entity460 HA in amplifying the pathological process involved in @entity0 .
