ERBB2 Targeting Reveals a Significant Suppression of Tumorigenesis in Murine Endometrial Cancer with Pten Mutation.

Abstract

Endometrial cancer is the most common gynecologic malignancy. PTEN is a negative regulator of PI3K signaling and is deficient in > 50% of primary human endometrial cancer. Amplification of ERBB2 promotes tumorigenesis and pathogenesis of several human cancers. However, the effect of ERBB2 targeting has not been studied in endometrial cancer with PTEN mutations. The murine model PgrErbb2Pten(Erbb2Pten) was developed to evaluate the effect of ERBB2 targeted therapy in endometrial cancer with PTEN deficiency. Histopathological and molecular analysis was performed for Ptenand Erbb2Ptenmice. Histopathological analysis revealed that Erbb2Ptenmice significantly reduced development and progression of endometrial cancer compared to Ptenmice. Furthermore, percentage of proliferative cells in Erbb2Ptenmice revealed anti-tumorigenic effect of Erbb2 ablation compared to Ptenmice. Our results demonstrate that Erbb2 ablation reveals a significant suppression of tumorigenesis on endometrial cancer of Ptenmice. Our results suggest that Erbb2 functions as an oncogene in endometrial cancer of Ptenmice implying that Erbb2 targeting can be used as an effective therapeutic approach for treatment of endometrial cancer with PTEN deficiency to hinder cancer development.