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Published on: January 12, 2020
Deregulated expression of Notch receptors in human hepatocellular carcinoma
1Department of Digestive Diseases, Wuhan General Hospital, Guangzhou Command PLA, Wuhan, Hubei Province, PR China.
Background And Aim:
Notch signaling controls cellular differentiation and proliferation. Deregulated expression of Notch receptors is observed in a growing number of malignant tumours, however, the role of Notch signaling in hepatocellular carcinoma is still unknown. To address this, the expression of Notch receptors in human hepatocellular carcinoma was examined in both protein and ribonucleic acid levels.
Patients And Methods:
Fifty-three hepatocellular carcinoma tissue sections were detected by immunohistochemistry. Three paired fresh surgical hepatocellular carcinoma and adjacent nontumour liver samples were analyzed by Western blot and reverse transcriptase polymerase chain reaction. Immunohistochemistry, Western blot and reverse transcriptase polymerase chain reaction are reliable methods to examine the expression of protein and RNA.
Results:
All of the four Notch receptors were expressed in the neoplastic cells of hepatocellular carcinoma tissues with different intensity and extensity. Notch1 and Notch4 were expressed in both cytoplasm and nucleus, and all of the nuclear staining showed up in the cytoplasm-positive cases. Cytoplasmic and nuclear Notch1 was detected in 88.7% (47/53) and 9.4% (5/53) of hepatocellular carcinoma tissues, respectively; positive rates of Notch4 were 67.9% (36/53) in cytoplasm and 52.8% (31/53) in nucleus. Notch2 and Notch3 were only in cytoplasm, with positive rates of 26.4% (14/53) and 52.8% (28/53), respectively. Compared with adjacent nontumour liver, Notch1 (cytoplasmic) and Notch4 (nuclear) were up-regulated (P<0.05, P<0.05), Notch2 was down-regulated (P<0.05), while Notch1 (nuclear), Notch3 and Notch4 (cytoplasmic) showed no difference between hepatocellular carcinoma and adjacent nontumour liver. Western blot and reverse transcriptase polymerase chain reaction analysis showed a consistent result.
Conclusion:
Our findings indicate that the expression of Notch receptors was deregulated and Notch signaling might be involved in the development of hepatocellular carcinoma.
Insights
Notch signaling is implicated in hepatocellular carcinoma development. This study found deregulated expression of Notch receptors in cancer tissues, suggesting their role in disease progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Notch signaling is crucial for cell differentiation and proliferation.
- Aberrant Notch receptor expression is linked to various cancers.
- The role of Notch signaling in hepatocellular carcinoma (HCC) remains unclear.
Purpose of the Study:
- To investigate the expression of Notch receptors in human HCC.
- To determine the potential involvement of Notch signaling in HCC development.
Main Methods:
- Immunohistochemistry (IHC) on 53 HCC tissue sections.
- Western blot and reverse transcriptase polymerase chain reaction (RT-PCR) on paired HCC and adjacent non-tumour liver samples.
- Analysis of all four Notch receptors (Notch1-4) at protein and RNA levels.
Main Results:
- All four Notch receptors were expressed in HCC cells.
- Notch1 (cytoplasmic) and Notch4 (nuclear) were significantly upregulated in HCC compared to non-tumour liver.
- Notch2 was downregulated in HCC, while Notch1 (nuclear), Notch3, and Notch4 (cytoplasmic) showed no significant difference.
- IHC, Western blot, and RT-PCR results were consistent.
Conclusions:
- Notch receptor expression is deregulated in hepatocellular carcinoma.
- Notch signaling pathways are likely involved in the pathogenesis of HCC.
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