Abstract
The aim of the present study was to investigate the expression and significance of transforming growth factor-β1 (TGF-β1) in the cytoplasm and extracellular matrix (ECM) of epithelial ovarian cancer cells. The expression of TGF-β1 protein was detected in paraffin-embedded sections of 25 normal ovarian epithelial tissues, 10 benign epithelial cysts and 72 epithelial ovarian cancer specimens, using the Strept Avidin Biotin Peroxidase Complex immunohistochemistry method. In addition, the expression of TGF-β1 mRNA in normal fibroblasts (NFs) and ovarian cancer-associated fibroblasts (CAFs) was assessed using semi-quantitative polymerase chain reaction (PCR). TGF-β1 protein was expressed in the cytoplasm and ECM, and no significant difference was identified between normal and benign ovarian tissues (P>0.05). However, the cytosolic expression of TGF-β1 declined gradually between the benign ovarian tumor and epithelial ovarian cancer, while its expression in the ECM significantly increased (P<0.05). The expression of TGF-β1 in the cytoplasm and ECM in epithelial ovarian cancer was found to negatively correlate with tumor differentiation, however, it was positively associated with the clinical stages. The positive rates of TGF-β1 in the cytoplasm and ECM between ovarian cancers in clinical stages I–II and III–IV were significantly different (P<0.05). Furthermore, the PCR data indicated that the relative expression of TGF-β1 mRNA in ovarian CAFs (1.0270±0.0539) was significantly higher than that in NFs (0.7131±0.0186). Therefore, the expression of TGF-β1 was identified to be associated with the development and progression of epithelial ovarian cancer, and the high expression of TGF-β1 in the ECM may be associated with the invasion and metastasis of ovarian cancer.
Highlights
The inhibitory effect of transforming growth factor‐β1 (TGF‐β1) on the growth of normal and early stage tumor cells is achieved via inhibition of the cell cycle progression from the G1 to the S phase
Alexandrow and Mose (3) reported that the treatment of numerous cell lines with Transforming growth factors (TGFs)‐β1 led to a rapid decrease in c‐myc mRNA and protein levels, while overexpression of the c‐myc protein antagonized the inhibitory effect of TGF‐β1 on cells entering the S phase
These results indicate that TGF‐β1 regulates c‐myc expression at the transcriptional and post‐transcriptional levels, thereby inhibiting the c‐myc‐regulated cell functions and arresting cell growth in the G1 phase
Summary
The initiation and development of a tumor involves multiple signaling pathways, including various aspects of cell proliferation, inhibition of apoptosis, tumor stroma and formation of peritumor blood vessels, which are all regulated by a variety of factors. The effect of cytokines on tumors has been the focus of attention. Transforming growth factors (TGFs), including TGF‐α and ‐β, are important factors that regulate cell growth and differentiation (1). TGF‐β1 inhibits tumor cell proliferation, it promotes tumor growth and invasion by modulating the tumor microenvironment, promoting the formation of tumor blood vessels and matrix, and suppressing the immune response. The present study detected the expression of TGF‐β1 in the cytoplasm and extracellular matrix (ECM) of epithelial ovarian cancer cells, to investigate the association between its expression, and the invasion and metastasis of ovarian cancer
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