PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes

Diabetes mellitus type 2 (T2DM) is a metabolic disease related to obesity, and both are characterized by insulin resistance, generally defined as a reduction in the capacity of insulin to exert its metabolic effects on tissues. A strong association between T2DM and certain types of cancer has been r...

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Main Authors:	Rivero, Donovan A., Zapata, Pedro, Ferri, Cristian A.
Format:	Online
Language:	English
Published:	Facultad de Ciencias Exactas, Químicas y Naturales 2024
Subjects:	Suppressor Gene Cancer Diabetes Mellitus Type 2 Gen Supresor Cáncer Diabetes Mellitus Tipo 2
Online Access:	https://www.fceqyn.unam.edu.ar/recyt/index.php/recyt/article/view/804

id	ojs-article-804
record_format	ojs
institution	Facultad de Ciencias Exactas Quimicas y Naturales
collection	Revista de Ciencia y Tecnologia RECyT
language	English
topic	Suppressor Gene Cancer Diabetes Mellitus Type 2 Gen Supresor Cáncer Diabetes Mellitus Tipo 2
spellingShingle	Suppressor Gene Cancer Diabetes Mellitus Type 2 Gen Supresor Cáncer Diabetes Mellitus Tipo 2 Rivero, Donovan A. Zapata, Pedro Ferri, Cristian A. PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes
topic_facet	Suppressor Gene Cancer Diabetes Mellitus Type 2 Gen Supresor Cáncer Diabetes Mellitus Tipo 2
format	Online
author	Rivero, Donovan A. Zapata, Pedro Ferri, Cristian A.
author_facet	Rivero, Donovan A. Zapata, Pedro Ferri, Cristian A.
author_sort	Rivero, Donovan A.
title	PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes
title_short	PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes
title_full	PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes
title_fullStr	PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes
title_full_unstemmed	PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes
title_sort	pten, a potential biomarker in susceptibility to cancer development in patients with diabetes
title_alt	PTEN, un Potencial Biomarcador en la Susceptibilidad al Desarrollo de Cáncer en Pacientes con Diabetes
description	Diabetes mellitus type 2 (T2DM) is a metabolic disease related to obesity, and both are characterized by insulin resistance, generally defined as a reduction in the capacity of insulin to exert its metabolic effects on tissues. A strong association between T2DM and certain types of cancer has been reported. The main reasons for this association could be due to hyperglycemia, the relationship between insulin resistance and hyperinsulinemia, or because the link is indirect and mediated by common risk factors such as obesity. The PTEN (phosphatase and tension homologue) gene on chromosome 10q23.3 was the first phosphatase characterized as a tumor suppressor gene. PTEN protein controls nutrient metabolism in the body and cell growth, so variations in protein expression are closely related to metabolism and the risk of developing cancer. PTEN exerts its tumor-suppressive effect by regulating phosphatidylinositol-3-kinase (PI3K). Through this kinase, intracellular signaling pathways of growth factors and insulin are connected. PI3K and, therefore, PTEN are involved in insulin's actions, and its signaling pathway is reduced in patients with T2DM. Possible causes of PTEN expression loss include mutations, genetic epigenetic silencing through promoter hypermethylation, and loss of heterozygosity at the PTEN locus. Hypermethylation of the PTEN promoter is considered an alternative mechanism of gene inactivation compared to mutations and deletions. In tumor cells, CpG regions of the promoters are methylated in most genes related to tumor suppressor activities and the control of normal cell growth. Gene "silencing" due to methylation in CpG islands allows the expression of oncogenes that trigger the carcinogenesis cascade. This study aims to evaluate the levels of gene and protein expression, as well as the methylation status of the PTEN promoter, as a biomarker for cancer development in patients with T2DM. For this purpose, healthy individuals, patients with diabetes, patients with cancer, and patients with both cancer and diabetes were recruited. Serum and whole blood samples were collected, and nucleic acids were extracted from total leukocytes. The degree of PTEN gene expression and the methylation status of the promoter were determined. Preliminary results showed that PTEN is overexpressed in individuals diagnosed with diabetes. Additionally, a higher degree of methylation of the PTEN promoter was observed in patients with both cancer and diabetes. These findings hold promise for understanding how PTEN mediates cancer development in patients with T2DM. Further studies could contribute to the development of more precise and personalized therapeutic approaches for cancer prevention and treatment in patients with T2DM.
publisher	Facultad de Ciencias Exactas, Químicas y Naturales
publishDate	2024
url	https://www.fceqyn.unam.edu.ar/recyt/index.php/recyt/article/view/804
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spelling	ojs-article-8042024-02-07T23:45:40Z PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes PTEN, un Potencial Biomarcador en la Susceptibilidad al Desarrollo de Cáncer en Pacientes con Diabetes Rivero, Donovan A. Zapata, Pedro Ferri, Cristian A. Suppressor Gene Cancer Diabetes Mellitus Type 2 Gen Supresor Cáncer Diabetes Mellitus Tipo 2 Diabetes mellitus type 2 (T2DM) is a metabolic disease related to obesity, and both are characterized by insulin resistance, generally defined as a reduction in the capacity of insulin to exert its metabolic effects on tissues. A strong association between T2DM and certain types of cancer has been reported. The main reasons for this association could be due to hyperglycemia, the relationship between insulin resistance and hyperinsulinemia, or because the link is indirect and mediated by common risk factors such as obesity. The PTEN (phosphatase and tension homologue) gene on chromosome 10q23.3 was the first phosphatase characterized as a tumor suppressor gene. PTEN protein controls nutrient metabolism in the body and cell growth, so variations in protein expression are closely related to metabolism and the risk of developing cancer. PTEN exerts its tumor-suppressive effect by regulating phosphatidylinositol-3-kinase (PI3K). Through this kinase, intracellular signaling pathways of growth factors and insulin are connected. PI3K and, therefore, PTEN are involved in insulin's actions, and its signaling pathway is reduced in patients with T2DM. Possible causes of PTEN expression loss include mutations, genetic epigenetic silencing through promoter hypermethylation, and loss of heterozygosity at the PTEN locus. Hypermethylation of the PTEN promoter is considered an alternative mechanism of gene inactivation compared to mutations and deletions. In tumor cells, CpG regions of the promoters are methylated in most genes related to tumor suppressor activities and the control of normal cell growth. Gene "silencing" due to methylation in CpG islands allows the expression of oncogenes that trigger the carcinogenesis cascade. This study aims to evaluate the levels of gene and protein expression, as well as the methylation status of the PTEN promoter, as a biomarker for cancer development in patients with T2DM. For this purpose, healthy individuals, patients with diabetes, patients with cancer, and patients with both cancer and diabetes were recruited. Serum and whole blood samples were collected, and nucleic acids were extracted from total leukocytes. The degree of PTEN gene expression and the methylation status of the promoter were determined. Preliminary results showed that PTEN is overexpressed in individuals diagnosed with diabetes. Additionally, a higher degree of methylation of the PTEN promoter was observed in patients with both cancer and diabetes. These findings hold promise for understanding how PTEN mediates cancer development in patients with T2DM. Further studies could contribute to the development of more precise and personalized therapeutic approaches for cancer prevention and treatment in patients with T2DM. La diabetes mellitus tipo 2 (DBTM2) es una enfermedad metabólica relacionada a la obesidad y ambas se caracterizan por un estado de resistencia a la insulina, generalmente definido como una reducción en la capacidad de la insulina para ejercer sus efectos metabólicos en los tejidos. Se ha reportado una fuerte asociación entre DBTM2 y determinados tipos de cáncer; las principales razones podrían deberse directamente a la hiperglucemia, la relación de la resistencia a la insulina y la hiperinsulinemia o a que la asociación es indirecta y mediada por factores de riesgo comunes a ambas condiciones, como por ejemplo la obesidad. El gen PTEN (phosphatase and tensin homologue) que se localiza en el cromosoma 10q23.3, fue la primera fosfatasa caracterizada como un gen supresor tumoral. La proteína PTEN controla el metabolismo de nutrientes en el organismo y el crecimiento celular, por lo cual variaciones en la expresión proteica está íntimamente relacionado al metabolismo y riesgo de contraer cáncer. PTEN ejerce su efecto supresor de tumores mediante la regulación del fosfatidilinositol-3-quinasa (PI3K). Es mediante esta quinasa que las vías de señalización intracelular de factores de crecimiento y de la insulina se relacionan. PI3K y por lo tanto PTEN, están involucrados en las acciones de la insulina, cuya vía de señalización se encuentra disminuida en pacientes con DBTM2. Las posibles causas de la pérdida de la expresión de PTEN incluyen mutaciones, epi-silenciamiento genético a través de la hipermetilación del promotor y una pérdida de la heterocigosidad en el locus de PTEN. La hipermetilación del promotor de PTEN es considerada como una alternativa a las mutaciones y deleciones como mecanismo de inactivación de genes. En células tumorales, las regiones CpG de los promotores se encuentran metiladas en la mayoría de los genes relacionados con actividades supresoras de tumores y de control del crecimiento celular normal. El “silenciamiento” génico debido a la metilación en las islas CpG permite la expresión de oncogenes que ponen en marcha la cascada de la carcinogénesis. El objetivo de este estudio es evaluar el nivel de expresión génica y proteica, así como el estado de metilación del promotor de PTEN, como biomarcador para el desarrollo de cáncer en pacientes con DBTM2. Para ello, se reclutaron individuos sanos, pacientes con diabetes, pacientes con cáncer y pacientes con cáncer y diabetes. Se tomaron muestras de sangre entera y los ácidos nucleicos fueron obtenidos a partir de los leucocitos totales. Se determinó el grado de expresión del gen PTEN y el estado de metilación del promotor. Los resultados preliminares obtenidos mostraron que PTEN se encuentra sobreexpresado en los individuos diagnosticados con diabetes, además, se observó un mayor grado de metilación del promotor de PTEN en los pacientes con cáncer y diabetes. Estos hallazgos son prometedores para comprender cómo PTEN interviene en el desarrollo de cáncer en los pacientes con DBTM2. Estudios posteriores podrían contribuir al desarrollo de enfoques terapéuticos más precisos y personalizados para la prevención y el tratamiento del cáncer en pacientes con DBTM2. Facultad de Ciencias Exactas, Químicas y Naturales 2024-02-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf text/html https://www.fceqyn.unam.edu.ar/recyt/index.php/recyt/article/view/804 Argentine Journal of Science and Technology; Vol. 40 No. Supl. 1 (2024); 38-39 Revista de Ciencia y Tecnología; Vol. 40 Núm. Supl. 1 (2024); 38-39 1851-7587 0329-8922 eng https://www.fceqyn.unam.edu.ar/recyt/index.php/recyt/article/view/804/836 https://www.fceqyn.unam.edu.ar/recyt/index.php/recyt/article/view/804/837 Derechos de autor 2023 Donovan A. Rivero, Pedro Zapata, Cristian A. Ferri https://creativecommons.org/licenses/by-nc/2.5/ar/

PTEN, a Potential Biomarker in Susceptibility to Cancer Development in Patients with Diabetes

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