Early placenta insulin-like growth factor ( @entity6353 ) is expressed by a subpopulation of the @entity1722 -positive SKBR3 @entity0 cell line displaying high motility and transendothelial invasiveness in vitro, as recently shown by our group. As a consequence of this, we established cellular models by generating an @entity6353 -overexpressing SKBR3 cell line, knocked down @entity6353 by adding specific small interfering RNA (siRNA) to those cells and produced @entity6353 -enriched and depleted serum-free culture media. @entity6353 -expressing cells as well as @entity6353 -induced SKBR3 cells acquired a high capacity for transendothelial invasiveness. We observed a thin and outspread morphology caused by enhanced formation of lamellipodia, i.e. protrusions in the initial phase of motility. In parallel, @entity1722 -positive MDAHer2 @entity0 cells also showed increased invasiveness when induced by @entity6353 -conditioned medium. A downstream signaling impact of @entity6353 could be observed in the form of reduced phosphorylation of @entity1722 , @entity1366 and akt, while phospholipase Cgamma1 phophorylation remained unaffected. As an in vivo model for highly motile @entity5 cells, Paget's disease of the nipple showed simultaneous @entity6353 and @entity1722 expression upon immunohistochemical examination using specific antibodies. Such experimental data have been translated to a clinical setting by using a prognostic tissue microarray established from 603 @entity0 cases. Survival data analysis found a significant association between expression levels of @entity6353 and 5-year overall survival that was dose dependent: @entity6353 (negative) 84%, @entity6353 (moderately positive) 77%, @entity6353 (strongly positive) 48% (P < 0.005). One particular subgroup (7.6% of the cases with full clinical records) that comprised @entity5 simultaneously expressing @entity6353 and @entity1722 represented @entity1 with the poorest 5-year overall survival. The results suggested that @entity6353 might be a @entity5 cell-produced growth factor that influences lateral @entity1722 signaling. Moreover, @entity6353 may be induced by factors apart from @entity1722 and may independently provide signaling for @entity5 invasion and motility.

Expression of early placenta insulin-like growth factor in XXXX cells provides an autocrine loop that predominantly enhances invasiveness and motility.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'tumors'] @entity6353 :: ('3641', 'Gene') :: ['EPIL'] @entity1366 :: ('5595;5594', 'Gene') :: ['erk1/2'] @entity1722 :: ('2064', 'Gene') :: ['Her2']
@entity0 :: (MESH:D001943,Disease) :: ['breast cancer']
