Alterations of UHRF Family Expression and UHRF1/ICBP90 Inhibits Phosphatase and Tensin Homolog Expression in
Masafumi Yoshimoto1, Aoi Tokuda1, Ayami Eguchi1,2
1Department of Oncology, Graduate School of Health Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Introduction:
The altered protein expression of inverted CCAAT box-binding protein of 90 kDa/ubiquitin-like with PHD and RING finger domains 1 (ICBP90/UHRF1) and Np95-like ring finger protein (NIRF)/UHRF2, which belong to the ubiquitin-like with PHD and RING finger domains (UHRF) family, is linked to tumor malignancy and the progression of various cancers. To determine the role of NIRF and ICBP90 in endometrial tumorigenesis, we evaluated ICBP90 and NIRF expression levels in endometrial cancers. Also molecular alterations of phosphatase and tensin homolog (PTEN) expression are the important event for endometrial carcinogenesis; therefore, we investigated the involvement between ICBP90 and PTEN expression.
Methods:
We used Western blot for NIRF, ICBP90, and PTEN expression, mutation analysis of NIRF gene, and immunohistochemical staining for the expression of NIRF and ICBP90. For immunohistochemical staining, we examined atypical endometrial hyperplasia, endometrial cancers, and noncancerous samples.
Results:
Our data showed that the reduced expression of NIRF and overexpression of ICBP90 occurred in atypical endometrial hyperplasia and endometrial cancer compared to the normal endometrium. The decrease in NIRF expression was significantly correlated with histological grade. Expression of ICBP90 was high, especially in the peripheral margin of a cancer nest. Western blot analysis of endometrial cancer cell lines referred an opposite correlation between ICBP90 and PTEN expression.
Conclusion:
Our findings suggested that continually overexpressed ICBP90 may contribute to the inhibition of PTEN expression, which is a frequent and important event in endometrial carcinogenesis. We propose that the reduced NIRF expression and ICBP90 overexpression is an early event in endometrial carcinogenesis; thus ICBP90 may be useful as a therapeutic target in this disease.
Insights
Altered expression of ICBP90 and NIRF proteins is linked to endometrial cancer. Overexpressed ICBP90 may inhibit PTEN, suggesting ICBP90 as a potential therapeutic target for endometrial cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Altered protein expression of ICBP90/UHRF1 and NIRF/UHRF2 is associated with cancer malignancy.
- Investigating the roles of NIRF and ICBP90 in endometrial tumorigenesis is crucial.
- PTEN alterations are significant in endometrial carcinogenesis.
Purpose of the Study:
- Evaluate ICBP90 and NIRF expression in endometrial cancers.
- Determine the relationship between ICBP90 and PTEN expression in endometrial carcinogenesis.
Main Methods:
- Western blot analysis for NIRF, ICBP90, and PTEN expression.
- Mutation analysis of the NIRF gene.
- Immunohistochemical staining of endometrial tissues (cancer, hyperplasia, normal).
Main Results:
- Reduced NIRF and overexpressed ICBP90 were observed in endometrial hyperplasia and cancer.
- Decreased NIRF expression correlated with histological grade.
- High ICBP90 expression was noted in cancer nests, with an inverse correlation to PTEN expression.
Conclusions:
- Overexpressed ICBP90 may inhibit PTEN, a key event in endometrial carcinogenesis.
- Reduced NIRF and overexpressed ICBP90 appear to be early events in endometrial cancer development.
- ICBP90 presents a potential therapeutic target for endometrial cancer.
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