To study the effect of hematopoietic progenitor kinase 1 (HPK1) up-regulation on the growth of xenografted human breast carcinoma cell lines MCF-7 and MDA-MB-231 in nude mice and underlying mechanism.

Breast cancer cell lines MCF-7 and MDA-MB-231 were subcutaneously injected into the left armpit fat pad of nude mice and transplanted tumor model. Nude mice were divided into six groups including MDA-MB-231 group, MDA-MB-231-con group and MDA-MB-231-HPK1 group, MCF-7 group, MCF-7-con group and MCF-7-HPK1 group. The tumor growth was observed and survival rate was analyzed. The expression of HPK1, c-Jun N-terminal kinase (JNK) and p53 in tumors was detected by immunohistochemistry, the expression of cysteinyl aspartate-specific protease (Caspase)-3 and Caspase-9 was investigated by Western blotting.

After transfection by HPK1, the tumor volumes (MDA-MB-231: F=86.61, P=0.001; MCF: F=26.48, P=0.001) were lower in HPK1 over-expression groups than that in control groupsof both cell lines and the survival rate of which was increased significantly (MDA-MB-231: χ²=5.315, P=0.021; MCF-7: χ²=4.909, P=0.027). Additionally, the expression of HPK1, JNK and p53 in the tumors tissues of nude mice in both overexpression groups was significantly up-regulated by immunohistochemistry, and there was a positive correlation trend. The expression of HPK1 and Caspase-3 proteins were significantly up-regulated in both overexpression groups (MDA-MB-231: P=0.005 and 0.023, respectively; MCF-7: P=0.033 and 0.016, respectively), but Caspase-9 protein was significantly up-regulated only in MCF-7-HPK1 group (P=0.027).

HPK1 overexpression could effectively lead to growth inhibition of xenografted human breast carcinoma cell lines MCF-7 and MDA-MB-231 in nude mice, followed by up-regulation of JNK, p53 and Caspase-3 and Caspase-9, which provides theoretical basis for molecular therapy of breast cell carcinoma.

Hematopoietic progenitor kinase 1; Breast cancer cell lines; Nude mice; Cell apoptosis