Abstract
Simple SummaryThe PTEN/AKT pathway is involved in several human and animal tumors’ pathogenesis. This study investigates the PTEN/AKT pathway’s biological and prognostic values in canine and feline mammary tumors. PTEN, phospho-AKT (p-AKT) and Rictor expression was determined by immunohistochemistry in canine mammary adenomas and carcinomas and feline mammary carcinomas. In mammary tumors of both species p-Akt was inversely correlated with PTEN expression and positively with Rictor expression; p-Akt and Rictor expression correlated with poorer prognosis. This data could provide a rationale for further studies of this pathway in veterinary oncology due to prognostic and therapeutic implications.Phosphatase and tensin homolog deleted on chromosome10 (PTEN), phospho-v-Akt murine thymoma viral oncogene homolog (AKT), and the Rapamycin-Insensitive Companion of mTOR (Rictor) expression was investigated by immunohistochemistry in 10 canine mammary adenomas (CMAs), 40 canine mammary carcinomas (CMCs), and 30 feline mammary carcinomas (FMCs). All the CMAs, 25 of 40 CMCs (63%) and 7 of 30 FMCs (23%), were PTEN-positive. In dogs, no CMAs and 15 of 25 CMCs (37%) expressed phospho-AKT (p-AKT), while 24 of 30 FMCs (82%) were p-AKT-positive. One of 10 CMAs (10%), 24 of 40 CMCs (60%) and 20 of 30 FMCs (67%) were Rictor-positive. In the dog, PTEN expression correlated with less aggressive tumors, absence of lymphatic invasion, and longer survival. P-AKT expression correlated with more aggressive subtype, lymphatic invasion, and poorer survival and Rictor expression with lymphatic invasion. In cats, PTEN correlated with less aggressive carcinomas, absence of lymphatic invasion, and better survival. P-AKT and Rictor expression correlated with poorer survival. PTEN expression was inversely correlated with p-AKT and Rictor in both species, while p-AKT positively correlated with Rictor expression. A strong PTEN/AKT pathway involvement in behavior worsening of CMT and FMTs is demonstrated, providing a rationale for further studies of this pathway in veterinary oncology.
Highlights
When phosphatidylinositol-3 kinase (PI3K) is activated by tyrosine kinase receptors, it phosphorylates PIP2 to generate PIP3 and activates the Akt murine thymoma viral oncogene homolog (AKT) signaling pathway
Due to the several pieces of evidence that confirm the role of the Phosphatase and tensin homolog deleted on chromosome10 (PTEN)/AKT pathway in various malignancies, including breast cancer, this study aimed to investigate its involvement in canine mamtumors (CMTs) and feline mammary carcinoma (FMC) by immunohistochemical analysis of PTEN, phospho-AKT
The purpose of our study is to investigate this pathway in these species and to evaluate the prognostic value of p-AKT and Rictor expression in these tumors
Summary
When phosphatidylinositol-3 kinase (PI3K) is activated by tyrosine kinase receptors, it phosphorylates PIP2 to generate PIP3 and activates the AKT signaling pathway. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) dephosphorylates PIP3 to PIP2 and negatively regulates the pathway. V-Akt murine thymoma viral oncogene homolog (AKT) is activated downstream of PIP3 and mediates physiological processes [1]. Mammalian Target of Rapamycin (mTOR) plays a vital role in phosphorylating AKT on Animals 2021, 11, 365 gene homolog (AKT) is activated downstream of PIP3 and mediates physiological processes [1]. Mammalian Target of Rapamycin (mTOR) plays a vital role in phosphorylating. 308 by the mTOR kinase from the mTOR 2complex 2 (mTORC2). Threonine by the mTOR kinase from the mTOR complex (mTORC2). Is a key component mTORC2,ofand it is required as demonstrated significant inhibicomponent mTORC2, and itfor is mTORC2 required function for mTORC2 function as by demonstrated by tion of the activation by RCTOR knockdown [3].knockdown
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