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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
Differential expression of activator protein-2 isoforms in renal cell carcinoma
Mototsugu Oya1, Shuji Mikami, Ryuichi Mizuno
1Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Objectives:
To investigate the expression of activator protein-2 (AP-2) in renal cell carcinoma (RCC) by immunohistochemistry. Three AP-2 isoforms alpha (alpha), beta (beta), and gamma (gamma) are known to exhibit a highly homologous structure; however, their functions are considered to be different. AP-2 has been implicated to play a role in carcinogenesis, as well as in the development of the kidney.
Methods:
The expression of the three AP-2 isoforms, alpha, beta, and gamma, was determined in 58 patients with RCC by immunohistochemistry. Epidermal growth factor receptor and erbB2 expression in 42 patients with RCC was also evaluated to investigate the correlation with AP-2 isoforms.
Results:
AP-2 isoforms are differentially expressed in normal renal tubules. Of 58 RCC tissue specimens, 15 (25.9%) demonstrated nuclear and cytoplasmic expression of AP-2alpha. Clear cell RCC had a significantly greater rate of AP-2alpha expression than the nonclear subtypes (14 of 41 clear versus 1 of 17 nonclear subtypes). Of the 58 specimens, 8 (13.8%) showed nuclear staining for AP-2beta; notably, localized small cases had a significantly greater rate of nuclear staining for AP-2beta (5 of 13 in pT1a versus 3 of 45 in pT1b or greater). In addition, only 2 cases (3.5%) demonstrated nuclear staining for AP-2gamma. Epidermal growth factor receptor and erbB2 expression did not correlate with expression of the AP-2 isoforms.
Conclusions:
AP-2 isoforms were differentially expressed in RCC, as well as in the adult normal kidney. AP-2alpha was dominantly expressed in clear cell RCC. AP-2beta expression was observed in the low-stage subtypes of RCC, and this transcription factor may be related to early carcinogenesis.
Insights
Activator protein-2 (AP-2) isoforms show varied expression in renal cell carcinoma (RCC). AP-2alpha is dominant in clear cell RCC, while AP-2beta is linked to early-stage carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Activator protein-2 (AP-2) is a transcription factor implicated in carcinogenesis and kidney development.
- Three AP-2 isoforms (alpha, beta, gamma) share structural homology but have distinct functions.
- Understanding AP-2 expression in renal cell carcinoma (RCC) is crucial for insights into tumorigenesis.
Purpose of the Study:
- To investigate the differential expression of AP-2 isoforms (alpha, beta, gamma) in renal cell carcinoma (RCC) using immunohistochemistry.
- To explore the correlation between AP-2 isoform expression and clinicopathological features of RCC.
- To assess the potential role of AP-2 in the early stages of kidney cancer development.
Main Methods:
- Immunohistochemistry was employed to evaluate the expression of AP-2alpha, AP-2beta, and AP-2gamma in 58 RCC tissue specimens.
- Expression levels of epidermal growth factor receptor and erbB2 were also assessed in a subset of 42 RCC patients.
- Statistical analysis was performed to determine correlations between AP-2 isoform expression and RCC subtypes and stages.
Main Results:
- AP-2 isoforms exhibited differential expression patterns in normal renal tubules and RCC tissues.
- AP-2alpha was significantly more expressed in clear cell RCC (25.9% overall, 14/41 clear cell) compared to non-clear cell subtypes (1/17).
- AP-2beta was detected in 13.8% of cases, with higher expression in localized, low-stage tumors (pT1a), suggesting a role in early carcinogenesis. AP-2gamma expression was minimal (3.5%).
Conclusions:
- AP-2 isoforms are differentially expressed in both normal adult kidneys and RCC.
- AP-2alpha is a dominant isoform in clear cell renal cell carcinoma.
- AP-2beta expression in early-stage RCC suggests its potential involvement in the initial phases of kidney cancer development.
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