| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T91696 | ||||
| Target Name | Fibronectin | ||||
| Target Type | Clinical Trial |
||||
| Action against Disease Model | AS1409 | Target of re-combinant protein drug. Xenograft studies in mice with prostate, colorectal and skin cancers have shown that AS1409 blocks cancer growth more effectively than an equivalent dose of untargeted IL12 | Drug Info | ||
| The Effect of Target Knockout, Knockdown or Genetic Variations | Fibronectin (Fn) plays an important part in the branching morphogenesis of salivary gland, lung, and kidney. Here, we examine the effect of the conditional knockout of Fn in themammary epitheli uM [Fn(MEp-/-)] on postnatal mammary gland development, using Cre-loxP-mediated gene knockout technology. Our data show that Fn deletion causes a moderate retardation in outgrowth and branching of the ductal tree in 5-week-old mice. These defects are partially compensated in virgin 16-week-old mice. However, mammary glands consisting of Fn-deficient epithelial cells fail to undergo normal lobuloalveolar differentiation during pregnancy. The severity of lobuloalveolar impairment ranged from lobular hypoplasia to aplasia in some cases and was associated with the amount of Fn protein recovered from these glands. Decreased rates of mammary epithelial cell proliferation accounted for delayed ductal outgrowth in virgin and lack of alveologenesis in pregnant Fn(MEp-/-) mice. Concomitant decreased expression of integrin beta(1) (Itgb1) and lack of autophosphorylation of focal adhesion kinase (Fak) suggest that this pathology might, at least in part, be mediated by disruption of the Fn/Itgb1/Fak signaling pathway. | ||||
| References | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.