We hypothesized that increased integrin activity due to loss of SHARPIN protein would affect the uptake of α<sub>v</sub>β<sub>3</sub>-selective cyclic, dimeric peptide <sup>68</sup>Ga-DOTA-E[c(RGDfK)]<sub>2</sub>, where E[c(RGDfk)]<sub>2</sub> = glutamic acid-[cyclo(arginyl-glycyl-aspartic acid-D-phenylalanine-lysine)], both in several tissue types and in the tumor microenvironment.
Furthermore, we investigated whether there is an association between the mRNA and protein expression levels of RBCK1, RNF31 and SHARPIN and clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status and found that RNF31 protein is significantly higher in ERalpha-negative tumors than ERalpha-positive tumors (p = 0.034).
These results are supported by our analysis of SIPL1 protein expression using a tissue microarray containing 224 breast cancer cases, in which higher levels of SIPL1 relate to ER+ and PR+ tumors and AKT activation.
Ectopic SIPL1 expression protected human U87 glioma cells from PTEN-mediated growth inhibition and promoted the formation of HeLa cell-derived xenograft tumors in immunocompromised mice.