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Dysregulation of PI3K/Akt/PTEN Pathway in Canine Mammary Tumor
Soo-Hyeon Kim1, Byung-Joon Seung1, Seung-Hee Cho1
1Department of Veterinary Pathology, College of Veterinary Medicine, Konkuk University, Seoul 05025, Korea.
Abstract:
The PI3K/Akt/PTEN axis is one of the most important signaling pathways in tumorigenesis. Recently, mutation of PIK3CA has been highlighted due to the similarities of mutational hotspots in both dogs and humans. PIK3CA H1047R (c.3140A > G) has been discovered as the most common mutational hot spot in canine mammary tumor in recent studies, while the feature of PIK3CA-mutated canine mammary tumor is obscure.
Methods:
A total of 83 mammary samples classified as normal (n = 13), adenoma (n = 25), low-grade carcinoma (n = 21), and high-grade carcinoma (n = 24) were included in this study. Genomic DNA from each sample was extracted, amplified by conventional PCR, and analyzed through Sanger sequencing. Analysis for the expression of PIK3CA, Akt, p-Akt, and PTEN was performed by immunohistochemistry, and of Akt2 by RNA in situ hybridization.
Results:
PIK3CA H1047R mutation was detected in 14.3% (10/70) of tumor samples. Dysregulation of p-Akt, Akt2, and PTEN was observed in mammary tumor samples, but only PTEN dysregulation was associated with PIK3CA H1047R mutation.
Conclusions:
The present study showed that dysregulation of components in the PI3K/Akt/PTEN pathway is a feature of canine mammary tumors, but this dysregulation is not directly correlated to the PIK3CA H1047R mutation except for PTEN expression.
Insights
The PI3K/Akt/PTEN pathway is altered in canine mammary tumors. While PIK3CA H1047R mutations are present, only PTEN expression changes correlate with this specific mutation in canine mammary cancer.
Area of Science:
- Oncology
- Molecular Biology
- Veterinary Medicine
Background:
- The PI3K/Akt/PTEN signaling pathway is crucial in tumorigenesis.
- PIK3CA mutations, particularly H1047R, are common in human and canine cancers.
- The characteristics of PIK3CA-mutated canine mammary tumors remain unclear.
Purpose of the Study:
- To investigate the PI3K/Akt/PTEN pathway alterations in canine mammary tumors.
- To determine the correlation between PIK3CA H1047R mutation and pathway component dysregulation.
Main Methods:
- Analysis of 83 canine mammary samples (normal, adenoma, low-grade carcinoma, high-grade carcinoma).
- Genomic DNA extraction, PCR amplification, and Sanger sequencing for PIK3CA mutation analysis.
- Immunohistochemistry for PIK3CA, Akt, p-Akt, PTEN expression and RNA in situ hybridization for Akt2.
Main Results:
- PIK3CA H1047R mutation found in 14.3% of tumor samples.
- Dysregulation of p-Akt, Akt2, and PTEN observed in mammary tumors.
- Only PTEN dysregulation was significantly associated with the PIK3CA H1047R mutation.
Conclusions:
- Dysregulation of the PI3K/Akt/PTEN pathway is a feature of canine mammary tumors.
- This pathway dysregulation is not directly linked to PIK3CA H1047R mutation, except for PTEN expression.
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