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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Cyclin G2 dysregulation in human oral cancer
Yong Kim1, Satoru Shintani, Yohko Kohno
1School of Dentistry and Dental Research Institute, University of California at Los Angeles, Los Angeles, California, USA.
Abstract:
Using expression microarray, we have previously shown that human cyclin G2 (hCG2) is significantly down-regulated in laser capture microdissected oral cancer epithelia. Western analysis showed detectable hCG2 protein in normal (2 of 2) but not in malignant (4 of 4) oral keratinocyte cell lines. Immunohistochemistry analysis done on oral cancers showed that normal oral mucosa (100%, 12 of 12) and 69.1% (47 of 68) of dysplastic oral epithelia expressed readily detectable hCG2 in the nuclei. However, only 11.1% of oral cancer epithelia (14 of 126) showed mild hCG2 nuclear staining. Interestingly, of the oral cancers devoid of nuclear hCG2 (112 cases), 58 cases (52%) showed cytoplasmic hCG2 immunostaining, whereas the other 54 cases (48%) exhibited neither nuclear nor cytoplasmic hCG2 staining. In vitro functional study by ectopic restoration of hCG2 expression in the human malignant squamous cell carcinoma (SCC) line SCC15 resulted in a significant inhibition of cellular proliferation (P < 0.001) and colony formation (P < 2 x 10(-5)) with increased population of G(1) phase and decreased in S phase (P < 0.01). Furthermore, stable down-regulation of hCG2 by short interference RNA-based gene silencing in immortalized normal oral keratinocytes resulted in enhanced cell growth with increase in S and prominently in G(2) phase. Because hCG2 has been implicated as a negative regulator in cell cycle progression, our results support that hCG2 dysregulation may play an important role in epithelial transformation and the early stages of human oral cancer development.
Insights
Human cyclin G2 (hCG2) is down-regulated in oral cancer, inhibiting proliferation and cell cycle progression. Loss of hCG2 promotes oral epithelial cell growth, suggesting its role in oral cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Human cyclin G2 (hCG2) was previously found to be significantly downregulated in oral cancer epithelia.
- hCG2 protein was detected in normal oral keratinocytes but absent in malignant cell lines.
Purpose of the Study:
- To investigate the role of hCG2 in oral cancer development and progression.
- To determine the functional impact of hCG2 on oral epithelial cell proliferation and cell cycle.
Main Methods:
- Expression microarray and Western blot analysis to assess hCG2 levels.
- Immunohistochemistry to evaluate hCG2 expression in oral tissues.
- In vitro studies involving ectopic hCG2 restoration and gene silencing using short interference RNA (siRNA).
Main Results:
- hCG2 was highly expressed in normal oral mucosa and dysplastic epithelia but significantly reduced in oral cancers.
- Restoring hCG2 expression in oral cancer cells inhibited proliferation and colony formation, causing G1 cell cycle arrest.
- Downregulating hCG2 in normal oral keratinocytes enhanced cell growth and altered cell cycle distribution.
Conclusions:
- Dysregulation of hCG2 is implicated in oral epithelial transformation and the early stages of oral cancer.
- hCG2 functions as a tumor suppressor by negatively regulating cell cycle progression.
- hCG2 may serve as a potential biomarker or therapeutic target for oral cancer.
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