The Research Of HMGA1 In Breast Cancer Tissue And MCF-7 Cells

Objective: To investigate the effect of HMGA1 on the proliferation, migration and invasion in human breast cancer MCF-7 cells,and to clarify the association of HMGA1 with the clinical parameter of breast cancer cancer.Methods: Human breast cancer MCF-7 cells were utilized in this study to investigate the effects of HMGA1 on the proliferation, migration and invasion. Experiments were divided into four parts. The first part is to investigate the effect of HMGA1 on the proliferation ability of MCF-7 cells. Cells were cultured(5,000 cells/well) and counted using an automated cell counter. For colony formation assay, cells were cultured(500 cells/well) and maintained for 7 days. The second part is to investigate the role of HMGA1 on the invasion ability of MCF-7 cells. For the invasion assays, 10,000 cells were resuspended in serum-free medium and placed in the upper chamber of a 24-well Matrigel? Invasion Chamber coated with Matrigel. Invasion cells were calculated as the percentage of total cells that had invaded the bottom chamber containing complete medium with serum. The third part is to unveil the effect of HMGA1 on the migration ability of MCF-7 cells. Cell migration was determined by the same method as invasion assay, except that Matrigel was omitted. The fourth part is to further indentify the association of HMGA1 with breast cancer progression. Two tissue microarrays, consisting 159 breast cancer cases and 32 normal cases and 50 paired cases of ductal breast cancer and corresponding lymph node metastasis were utilized. The tissues were histologically interpretable and analyzed for the correlation with clinicopathological parameters by immno-histochemistry.Results: 1) HMGA1 enhances the proliferation ability of breast cancer cells. The elevated expression of HMGA1 in the MCF-7 cells led to an obvious enhancement of the proliferation and colony-forming ability. 2) It was observed that the higher expression of HMGA1 in the MCF-7 cells markedly promoted cell migration and invasion.3)The tissue microarray analysis revealed that HMGA1 was expressed in 62.3 and 46.9% of the breast tumor tissues and matched breast cancer adjacent tissues, respectively, predominantly in the nucleus. Furthermore, statistical analysis confirmed that breast cancer tissues with a higher expression of human epidermal growth factor receptor 2(HER2) showed a higher expression level of HMGA1(P=0.007) and that a higher expression level of HMGA1 was also found in the ductal breast cancer tissues compared with the lobular breast cancer tissues(P=0.001). These tissue microarray data suggest that a differential expression of HMGA1 exists in various types of breast cancer. It was found that 76% of the ductal breast cancer cases showed HMGA1 positive staining and 90% of the paired lymph node samples showed an expression of HMGA1, although statistical analysis showed no significance(P=0.088).Conclusion: 1) HMGA1 enhances the proliferation,migration and invasion ability of breast cancer cells. 2)The breast cancer tissues with a high expression of human epidermal growth factor receptor 2(HER2) showed a higher expression level of HMGA1 and a higher expression level of HMGA1 was found in the ductal breast tumors compared with those in lobular breast cancer.