HE7 is a serine/threonine kinase identified through gene expression profiling of the tumorigenic cervical cancer cell line HeLa and its non-tumorigenic derivative HeLa/HF cells. It is expressed at higher level in HeLa cells, suggesting its pro-survival function. We have used siRNA mediated down-regulation of HE7 to assess its potential function in cell survival. RNAi mediated HE7 down-regulation induces cell apoptosis and reduces both anchorage-dependent and anchorage-independent growth. Using a unique inducible RNAi vector we developed, we created a novel xenograft tumor model, in which tumors are established under non-induced conditions, followed by induced target inactivation upon the oral dosing of inducer. We demonstrated a staged tumor regression response to the induced HE7 silencing. For early staged tumors, HE7 inactivation caused dramatic tumor regression (100% regresses and 50% becomes tumor-free). Later staged tumors also demonstrated significant responses (75% regression). Our results support the utility of this new inducible xenograft tumor model for efficacy evaluation of cancer target; and our data also provides a robust in vivo efficacy validation of HE7 as a novel cancer therapeutic target. Currently, we are developing assays to screen HE7 inhibitors.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]