Ack1 in breast and prostate cancer 

One of the major physiological functions of Activated Ack1 appears to be in various hormonally regulated cancers, e.g. prostate, breast and pancreatic cancers.

Ack1/AKT signaling in Breast cancer

Mahajan K et al. PLoS One. 2010;5(3):e9646

 

(A) TMA sections representing different breast cancer stages stained with pTyr284-Ack1 and pTyr176-AKT antibodies. (B) Box plots to summarize distributions of staining intensities for pTyr284-Ack1 in different stages of breast cancer. A significant increasing trend of intensity across progression stages was detected (Mantel-Haenszel test, p = 0.02). The box has lines at the lower quartile (25%), median (50%), and upper quartile values (75%) while the red-cross within the circle marks the mean value. Whiskers extend from each end of the box to the most extreme values within 1.5 times the interquartile range from the ends of the box. The data with values beyond the ends of the whiskers, displayed with black circles, are potential outliers. (C) Box plots to summarize distributions of staining intensities for pTyr176-AKT in different stages of breast cancer. A significant increasing trend of intensity across progression stages was detected (Mantel-Haenszel test, p<0.0001). (D) Kaplan–Meier analysis shows that individuals with breast cancer that have moderate to strong staining (>4) of pTyr284-Ack1 have a lower probability of survival (log rank test, p = 0.08). (E) Kaplan–Meier analysis of the breast cancer patients that have moderate to strong staining (>4) of pTyr176-AKT have significantly lower probability of survival (log rank test, p = 0.02).

Ack1/AKT signaling in Prostate cancer

Mahajan K et al. Prostate.2010(Manuscript in press)

pTyr284-Ack1 expression correlates positively with disease progression and negatively with survival of prostate cancer patients. A:TMA sections representing different prostate cancer stages were stained with pTyr284-Ack1antibodies.B: Box plots to summarize distributions of staining intensities for pTyr284-Ack1in different stages of prostate cancer. The box has lines at the lower quartile (25%),median (50%), and upper quartile values (75%),while the red cross within the circle marks the mean value. Whiskers extend from each end of the box to the most extreme values within 1.5 times the inter quartile range from the ends of the box. The data with values beyond the ends of the whiskers, displayed with black circles, are potential outliers. A significant increase in expression of Tyr284-phosphorylated Ack1 (Spearman’s rank correlation coefficient=0.32, P<0.0001) was seen as prostate cancer progressed. C:Kaplan-Meier survival curves shows that individuals with prostate cancer that have moderate to strong staining of pTyr284-Ack1(>2)have a significantly worse overall survival outcome than those with lower pTyr284-Ack1levels (log-rank P=0.041).