The Controversy Around Callous MEK inhibitor-Practices

Our results suggest that PTPN12 functions as a suppressor of malignant transformation and may be inactivated in TNBC. Given the deletions and sequence alterations in PTPN12, we wished to?test whether PTPN12 function may also be frequently compromised by loss of expression. Unfortunately, PTPN12 mRNA expression is high in stromal compartments, thus precluding the use of RNA profiling to evaluate PTPN12 levels in public breast cancer data sets. To circumvent this problem we developed a specific immunohistochemical assay for PTPN12 protein (Figure?S5A) and evaluated expression of PTPN12 in an independent cohort of 185 breast cancers. PTPN12 protein was consistently expressed in normal breast tissue (Figure?S5B). In contrast, PTPN12 was MEK inhibitor drugs undetectable in 37% of invasive breast cancers (example images shown in Figure?4I and Figure?S5C). Strikingly, loss of PTPN12 expression occurred most frequently in TNBC (60.4% of TNBCs exhibit no detectable PTPN12 protein) (Figure?4J). In contrast, HER2-amplified tumors only rarely exhibited loss of PTPN12 expression (9.1% of HER2-amplified tumors). The near-mutual exclusivity of HER2 amplification and PTPN12 loss (p?Autophagy and HER2/EGFR RTKs operate in the same genetic pathway. Collectively, these results indicate that PTPN12 is frequently inactivated by deletion, this website sequence variation, or loss of protein expression, and PTPN12 loss of function may be a major determinant in aggressive TNBC. Our observation that PTPN12 protein levels were frequently undetectable in primary human breast cancers led to us to examine the mechanism(s) by which PTPN12 expression is lost. By examining other suppressors of HMEC transformation, we observed that the tumor suppressor REST was also lost in primary breast cancers (example images in Figure?5A), and the expression of REST and PTPN12 was highly correlated (p?