| Objective:Endometrial carcinoma is one of the three worst cancers in female reproductive system. The incidence rate has increased worldwide in rescent years. The biological behavior of malignant tumor is closely associated with its special material metabolism and energy metabolism. The metabolic research on tumor-associated fatty acid started from the1990s. The significantly enhanced lipogenesis is a metabolic hallmark of rapidly proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than90%of required lipids de novo. The sterol regulatory element-binding protein1(SREBP1), encoded by SREBF1gene, is a master regulator of lipogenic gene expression. Even though it is known that SREBP1and its target genes are overexpressed in a variety of cancers, such as colorectal carcinoma, breast cancer, prostate cancer and hepato carcinoma, the role of SREBP1in endometrial cancer is largely unknown. Herein, we detect the expression of SREBP1in normal endometrium and endometrial cancer through immunohistochemical staining and expore the relationship between the expression of SREBP1in endometrial cancer and its clinical pathological features.Then we explore its influence on the biological behavior of endometrial cancer cell by SREBP1short hairpin RNA.Furthermore, providing a new thinking for targeted therapy of endometrial cancer.Methods:Tissue microarray and Immunohistochemical staining were used to detect the expression and cellular localization of SREBP1in120endometrial cancers specimens and41matched normal endometrium specimens, so as to the52cases with proliferative phase,56cases with secretory phase and51cases with post-menopause phase of normal endometrium,18cases with hyperplasia endometrial and11cases with atypical hyperplasia endometrial. Quantitative real-time polymerase chain reaction and western blot were used to detect the level of mRNA and protein in five different endometrial cancer cell lines, then we chose low differentiated AN3-CA cell line to construct SREBP1shRNA stable cell line. Cell proliferation, cell cycle, cell invasion, cell colony-forming test and nude mice transplant tumor experiment were conducted to analyze the influence of SREBP1shRNA on cell biological behavior.Results:(1) SREBP1expression was gradually reduced in proliferative phase, secretive phase and post-menopause phase of normal endometrium, There was a significant difference among these groups (P<0.05)(2) SREBP1was low expressed and mainly localized in cytoplasm in matched normal endometrium, while it was overexpressed and localized in nuclear and cytoplasm in endometrial cancer. There was a significant difference between these two groups in Immunohistochemical staining H-Score ratings of cytoplasm, nuclear, and whole tissue (P<0.05)(3) SREBP1expression was gradually enhanced in highly differentiated to low differentiated endometrial cancer, There was a significant difference among these groups (P<0.05)(4) Compared with the control group,SREBPl shRNA can reduce AN3-CA cell proliferation, invasion, and cell colony-forming capacity, induce cell apoptosis, and inhibit nude mice transplant tumor formation ability,there was a significant difference (P<0.05),but there was no significant influence on cell cycle (P>0.05) Conclusion: (1) SREBP1was overexpressed in endometrial cancer, and was associated with tumor differentiation degree. Its overexpression and activation may play a key role in the progression of endometrial cancer.(2) SREBP1shRNA could reduce cell proliferation, invasion and cell colony forming capacity, induce cell apoptosis, and inhibit nude mice transplant tumor formation ability indicating that endogenous SREBP1was involved in the progression and metastasis of endometrial cancer, thus providing a theoretical basis on potential molecular target therapy for endometrial cancer. |
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