Expression Of HPIP In Gastric Cancer: A Clinical And Experimental Study

Human hematopoietic PBX-interacting protein(HPIP) was first identified by Abramovich in fetal liver cDNA library with a Yeast two hybridization strategy using pre-B-cell leukemia transcription factor1(PBX1) as a bait in2000. It plays an important role in the regulation of hematopoietic stem cell differentiation and the inhibition of leukemia generation via inhibiting the transcription activation of E2A-PBX1. Recent studies reveal that the transfection of exogenous HPIP can greatly promote the growth of tumor cells, and this indicates that HPIP may participate in the proliferation of tumor cell. Gastric carcinoma (GC) is probably the most serious malignant tumor in human beings. Early diagnose of GC was based on the tumor makers such as MG7antigen, carcinoma embryonic antigen CEA, but this strategy usually has a low sensitivity (probably10-40%) and specificity. In this work, we studied the expression levels of HPIP in carcinoma tissues and cell lines as well as the related mechanisms so as to exploring new tumor makers for GCResection tissues of carcinoma obtained from Beijing Cancer Hospital was assayed with immunohistochemistry to detect the levels of HPIP in GC and adjacent respectively, and HPIP in GC cell lines was determined by western blotting. Cells with overexpression or deletion of HPIP were obtained to investigate the effect of HPIP on the anchorage dependent or independent growth of GC cells. What’s more, the correlation of the expression of p53,p21and HPIP was also carried out in related clinical data. Immunohistochemistry assay turned out that higher level of HPIP was identified in GC than normal tissues, and there exist correlation between the level of HPIP and pathological types or differentiation. The expression of HPIP in signet ring cell carcinoma was much higher than other carcinoma types. High HPIP levels was observed in BGC823and SGC7901cells, while nearly no expression expression in MGC803and MKN28cells. Stable cell line with overexpression or knockdown of HPIP was obtained via transient transfection in BGC823and SGC7901cells. And cell growth assay reveals that overexpression of HPIP promote cell growth while Knockout of HPIP regress growth. The promotion effect of HPIP on the anchorage dependent or independent growth of GC cells was also observed. And the assay of clinical data revealed that no correlation was observed between the expression of p53,p21and HPIP in GC.In all, HPIP probably involved in the carcinogenesis of gastric and could be used as a potential molecular maker for GC diagnose. While further study should be carried out to explore the concrete mechanisms of HPIP in GC so as to develop a new candidate molecular target of gene therapy for GC with HPIP.