Abstract. βig-h3 is an extracellular matrix protein and its expression is highly induced by transforming growth factor (TGF-β). It has also been suggested to play an important role in the growth and invasion of colon and pancreatic cancers. In the present study, we demonstrated that βig-h3 is expressed in mesothelial cells, especially in patients with advanced gastric cancer. The positive rate of βig-h3 was significantly higher in cases with a more invasive and advanced serous-type, with visible peritoneal metastasis, and in peritoneal lavage cytological examination (PLC) (+) and peritoneal lavage fluid CEA mRNA(+) subgroups (p<0.05). Our study also showed that the expression of βig-h3 gradually increased with increasing TGF-β1 concentrations in vitro in a time-dependant manner. In addition, βig-h3 also induced human gastric carcinoma cell line (SGC-7901) cell adhesion in a dose-dependent manner and significantly increased cell migration and proliferation. The results suggest that βig-h3 expression in peritoneal mesothelial cells in gastric cancer patients is a marker of the biological behavior of gastric cancer and plays an important role in the process of peritoneal carcinomatosis.
BackgroundRAP80 is a member of BRCA1-A complex, which plays an important role in regulating the cell cycle checkpoint and DNA damage repair in the nucleus.MethodWe investigated RAP80 expression in breast cancer and its paired normal breast tissues to further analyze its role in the biological behavior of breast cancer cells.ResultsRAP80 expression in breast cancer (62.3%, 101/162) was significantly lower than that in adjacent normal breast tissues (P<0.05). RAP80 expression was related to tumor size, lymph node metastasis, TNM stage, and molecular subtype (P<0.05). RAP80 mRNA expression was significantly lower in triple-negative breast cancer than other types. The mRNA and protein of RAP80 were obvious in MCF-7 and very weak in ZR-75 or MDA-MB-231, so we picked MCF-7 to be transfected with RAP80 siRNA. The survival rate of both cells decreased in a dose-dependent manner and the IC50 value for cisplatin in MCF-7 RAP80 siRNA cells was 0.83 µg/mL, and 1.69 µg/mL in wild-type MCF-7 according to MTT. RAP80 siRNA transfection upregulated the apoptosis and downregulated invasive or migrating ability of MCF-7. RAP80 siRNA also upregulated the protein expression of Caspase-3, cleaved Caspase-3, Apaf-1, Cytochrome C, Bax, and Fas, and downregulated the protein expression of Bcl-2.ConclusionRAP80 expression was related to ER or PR activity. Inhibition of RAP80 expression can induce apoptosis in breast cancer cells and improve chemosensitivity to cisplatin. Tumor cells can activate protective responses to inhibit cell cycle progression, which may be related to RAP80, and repair cisplatin-induced DNA damage. RAP80 is related to BRCA1’s effect, which can be used as an interesting target for pharmacological modulation that can increase the efficiency of cisplatin chemotherapy.
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