The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Monica Fedele - One of the best experts on this subject based on the ideXlab platform.
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HMGA2 cooperates with either p27kip1 deficiency or Cdk4R24C mutation in pituitary tumorigenesis
2018Co-Authors: Monica Fedele, Orlando Paciello, Davide De Biase, Mario Monaco, Gennaro Chiappetta, Michela Vitiello, Antonio Barbieri, Domenica Rea, Antonio Luciano, Serenella PapparellaAbstract:We have previously reported a critical role of HMGA proteins in pituitary tumorigenesis since either the Hmga1 or Hmga2 gene overexpression/activation induces the development of mixed growth hormone/Prolactin Cell pituitary adenomas by activating the E2F transcription factor 1, and then enhancing the G1/S transition of the Cell cycle. Consistently, amplification and overexpression of the HMGA2 gene was found in human pituitary Prolactinomas. Since impairment of the Cell cycle control represents a feature of experimental and human pituitary adenomas, we have investigated the possible synergism between the alterations of other Cell cycle regulators, such as p27 deficiency or Cdk4R24C mutation, with Hmga2 overexpression in pituitary tumorigenesis. Therefore, we crossed the Hmga2/T mice, overexpressing the truncated/active form of the Hmga2 gene, either with the knockout mice for p27kip1, or with the knockin mice for the Cdk4R24C mutation, both developing pituitary adenomas. Increased incidence and decreased latency in the development of pituitary lesions appeared in double mutant Hmga2/T;Cdk4R24C mice, and increased features of invasiveness and atypia were observed in pituitary tumors of both Hmga2/T;p27-ko and Hmga2/T;Cdk4R24C double mutant mice as compared with single mutant compounds. Interestingly, most of these mice develop pituitary adenomas with high Ki67 index, extrasellar expansion and brain tissue infiltration, representing good mouse models for human aggressive pituitary adenomas. Taken together, the results reported here indicate a cooperation between HMGA2 overexpression and either p27kip1 or CDK4 impairment in promoting pituitary tumor development and progression.
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transgenic mice overexpressing the wild type form of the hmga1 gene develop mixed growth hormone Prolactin Cell pituitary adenomas and natural killer Cell lymphomas
Oncogene, 2005Co-Authors: Monica Fedele, Francesca Pentimalli, Gustavo Baldassarre, Sabrina Battista, Andres J Kleinszanto, Lawrence C Kenyon, Rosa Visone, Ivana De Martino, Andrea Ciarmiello, Claudio ArraAbstract:Overexpression of HMGA1 proteins is a constant feature of human carcinomas. Moreover, rearrangements of this gene have been detected in several human benign tumors of mesenchymal origin. To define the role of these proteins in Cell transformation in vivo, we have generated transgenic mice overexpressing ubiquitously the HMGA1 gene. These mice developed mixed growth hormone/Prolactin Cell pituitary adenomas and natural killer (NK)-T/NK Cell lymphomas. The HMGA1-induced expression of IL-2 and IL-15 proteins and their receptors may account for the onset of these lymphomas. At odds with mice overexpressing a wild-type or a truncated HMGA2 protein, adrenal medullar hyperplasia and pancreatic islet Cell hyperplasia frequently occurred and no increase in body size and weight was observed in HMGA1 mice. Taken together, these data indicate an oncogenic role of the HMGA1 gene also in vivo.
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Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas.
Oncogene, 2002Co-Authors: Monica Fedele, Gustavo Baldassarre, Sabrina Battista, Lawrence C Kenyon, Rosa Visone, Vincenzo Fidanza, Andres J. Klein-szanto, Albert F. Parlow, Giovanna Maria Pierantoni, Eric OutwaterAbstract:Overexpression of the HMGA2 gene is a common feature of neoplastic Cells both in experimental and human models. Intragenic and extragenic HMGA2 rearrangements responsible for HMGA2 gene overexpression have been frequently detected in human benign tumours of mesenchymal origin. To better understand the role of HMGA2 overexpression in human tumorigenesis, we have generated transgenic mice carrying the HMGA2 gene under the transcriptional control of the cytomegalovirus promoter. High expression of the transgene was demonstrated in all the mouse tissues analysed, whereas no expression of the endogenous HMGA2 gene was detected in the same tissues from wild-type mice. In this study, two independent lines of transgenic mice have been generated. By 6 months of age, 85% of female animals of both transgenic lines developed pituitary adenomas secreting Prolactin and growth hormone. The transgenic males developed the same phenotype with a lower penetrance (40%) and a longer latency period (about 18 months). Therefore, these data demonstrate that the overexpression of HMGA2 leads to the onset of mixed growth hormone/Prolactin Cell pituitary adenomas. These transgenic mice may represent an important tool for the study of this kind of neoplasia.
Eric Outwater - One of the best experts on this subject based on the ideXlab platform.
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Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas.
Oncogene, 2002Co-Authors: Monica Fedele, Gustavo Baldassarre, Sabrina Battista, Lawrence C Kenyon, Rosa Visone, Vincenzo Fidanza, Andres J. Klein-szanto, Albert F. Parlow, Giovanna Maria Pierantoni, Eric OutwaterAbstract:Overexpression of the HMGA2 gene is a common feature of neoplastic Cells both in experimental and human models. Intragenic and extragenic HMGA2 rearrangements responsible for HMGA2 gene overexpression have been frequently detected in human benign tumours of mesenchymal origin. To better understand the role of HMGA2 overexpression in human tumorigenesis, we have generated transgenic mice carrying the HMGA2 gene under the transcriptional control of the cytomegalovirus promoter. High expression of the transgene was demonstrated in all the mouse tissues analysed, whereas no expression of the endogenous HMGA2 gene was detected in the same tissues from wild-type mice. In this study, two independent lines of transgenic mice have been generated. By 6 months of age, 85% of female animals of both transgenic lines developed pituitary adenomas secreting Prolactin and growth hormone. The transgenic males developed the same phenotype with a lower penetrance (40%) and a longer latency period (about 18 months). Therefore, these data demonstrate that the overexpression of HMGA2 leads to the onset of mixed growth hormone/Prolactin Cell pituitary adenomas. These transgenic mice may represent an important tool for the study of this kind of neoplasia.
Gustavo Baldassarre - One of the best experts on this subject based on the ideXlab platform.
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transgenic mice overexpressing the wild type form of the hmga1 gene develop mixed growth hormone Prolactin Cell pituitary adenomas and natural killer Cell lymphomas
Oncogene, 2005Co-Authors: Monica Fedele, Francesca Pentimalli, Gustavo Baldassarre, Sabrina Battista, Andres J Kleinszanto, Lawrence C Kenyon, Rosa Visone, Ivana De Martino, Andrea Ciarmiello, Claudio ArraAbstract:Overexpression of HMGA1 proteins is a constant feature of human carcinomas. Moreover, rearrangements of this gene have been detected in several human benign tumors of mesenchymal origin. To define the role of these proteins in Cell transformation in vivo, we have generated transgenic mice overexpressing ubiquitously the HMGA1 gene. These mice developed mixed growth hormone/Prolactin Cell pituitary adenomas and natural killer (NK)-T/NK Cell lymphomas. The HMGA1-induced expression of IL-2 and IL-15 proteins and their receptors may account for the onset of these lymphomas. At odds with mice overexpressing a wild-type or a truncated HMGA2 protein, adrenal medullar hyperplasia and pancreatic islet Cell hyperplasia frequently occurred and no increase in body size and weight was observed in HMGA1 mice. Taken together, these data indicate an oncogenic role of the HMGA1 gene also in vivo.
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Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas.
Oncogene, 2002Co-Authors: Monica Fedele, Gustavo Baldassarre, Sabrina Battista, Lawrence C Kenyon, Rosa Visone, Vincenzo Fidanza, Andres J. Klein-szanto, Albert F. Parlow, Giovanna Maria Pierantoni, Eric OutwaterAbstract:Overexpression of the HMGA2 gene is a common feature of neoplastic Cells both in experimental and human models. Intragenic and extragenic HMGA2 rearrangements responsible for HMGA2 gene overexpression have been frequently detected in human benign tumours of mesenchymal origin. To better understand the role of HMGA2 overexpression in human tumorigenesis, we have generated transgenic mice carrying the HMGA2 gene under the transcriptional control of the cytomegalovirus promoter. High expression of the transgene was demonstrated in all the mouse tissues analysed, whereas no expression of the endogenous HMGA2 gene was detected in the same tissues from wild-type mice. In this study, two independent lines of transgenic mice have been generated. By 6 months of age, 85% of female animals of both transgenic lines developed pituitary adenomas secreting Prolactin and growth hormone. The transgenic males developed the same phenotype with a lower penetrance (40%) and a longer latency period (about 18 months). Therefore, these data demonstrate that the overexpression of HMGA2 leads to the onset of mixed growth hormone/Prolactin Cell pituitary adenomas. These transgenic mice may represent an important tool for the study of this kind of neoplasia.
Sabrina Battista - One of the best experts on this subject based on the ideXlab platform.
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transgenic mice overexpressing the wild type form of the hmga1 gene develop mixed growth hormone Prolactin Cell pituitary adenomas and natural killer Cell lymphomas
Oncogene, 2005Co-Authors: Monica Fedele, Francesca Pentimalli, Gustavo Baldassarre, Sabrina Battista, Andres J Kleinszanto, Lawrence C Kenyon, Rosa Visone, Ivana De Martino, Andrea Ciarmiello, Claudio ArraAbstract:Overexpression of HMGA1 proteins is a constant feature of human carcinomas. Moreover, rearrangements of this gene have been detected in several human benign tumors of mesenchymal origin. To define the role of these proteins in Cell transformation in vivo, we have generated transgenic mice overexpressing ubiquitously the HMGA1 gene. These mice developed mixed growth hormone/Prolactin Cell pituitary adenomas and natural killer (NK)-T/NK Cell lymphomas. The HMGA1-induced expression of IL-2 and IL-15 proteins and their receptors may account for the onset of these lymphomas. At odds with mice overexpressing a wild-type or a truncated HMGA2 protein, adrenal medullar hyperplasia and pancreatic islet Cell hyperplasia frequently occurred and no increase in body size and weight was observed in HMGA1 mice. Taken together, these data indicate an oncogenic role of the HMGA1 gene also in vivo.
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Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas.
Oncogene, 2002Co-Authors: Monica Fedele, Gustavo Baldassarre, Sabrina Battista, Lawrence C Kenyon, Rosa Visone, Vincenzo Fidanza, Andres J. Klein-szanto, Albert F. Parlow, Giovanna Maria Pierantoni, Eric OutwaterAbstract:Overexpression of the HMGA2 gene is a common feature of neoplastic Cells both in experimental and human models. Intragenic and extragenic HMGA2 rearrangements responsible for HMGA2 gene overexpression have been frequently detected in human benign tumours of mesenchymal origin. To better understand the role of HMGA2 overexpression in human tumorigenesis, we have generated transgenic mice carrying the HMGA2 gene under the transcriptional control of the cytomegalovirus promoter. High expression of the transgene was demonstrated in all the mouse tissues analysed, whereas no expression of the endogenous HMGA2 gene was detected in the same tissues from wild-type mice. In this study, two independent lines of transgenic mice have been generated. By 6 months of age, 85% of female animals of both transgenic lines developed pituitary adenomas secreting Prolactin and growth hormone. The transgenic males developed the same phenotype with a lower penetrance (40%) and a longer latency period (about 18 months). Therefore, these data demonstrate that the overexpression of HMGA2 leads to the onset of mixed growth hormone/Prolactin Cell pituitary adenomas. These transgenic mice may represent an important tool for the study of this kind of neoplasia.
Lawrence C Kenyon - One of the best experts on this subject based on the ideXlab platform.
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transgenic mice overexpressing the wild type form of the hmga1 gene develop mixed growth hormone Prolactin Cell pituitary adenomas and natural killer Cell lymphomas
Oncogene, 2005Co-Authors: Monica Fedele, Francesca Pentimalli, Gustavo Baldassarre, Sabrina Battista, Andres J Kleinszanto, Lawrence C Kenyon, Rosa Visone, Ivana De Martino, Andrea Ciarmiello, Claudio ArraAbstract:Overexpression of HMGA1 proteins is a constant feature of human carcinomas. Moreover, rearrangements of this gene have been detected in several human benign tumors of mesenchymal origin. To define the role of these proteins in Cell transformation in vivo, we have generated transgenic mice overexpressing ubiquitously the HMGA1 gene. These mice developed mixed growth hormone/Prolactin Cell pituitary adenomas and natural killer (NK)-T/NK Cell lymphomas. The HMGA1-induced expression of IL-2 and IL-15 proteins and their receptors may account for the onset of these lymphomas. At odds with mice overexpressing a wild-type or a truncated HMGA2 protein, adrenal medullar hyperplasia and pancreatic islet Cell hyperplasia frequently occurred and no increase in body size and weight was observed in HMGA1 mice. Taken together, these data indicate an oncogenic role of the HMGA1 gene also in vivo.
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Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas.
Oncogene, 2002Co-Authors: Monica Fedele, Gustavo Baldassarre, Sabrina Battista, Lawrence C Kenyon, Rosa Visone, Vincenzo Fidanza, Andres J. Klein-szanto, Albert F. Parlow, Giovanna Maria Pierantoni, Eric OutwaterAbstract:Overexpression of the HMGA2 gene is a common feature of neoplastic Cells both in experimental and human models. Intragenic and extragenic HMGA2 rearrangements responsible for HMGA2 gene overexpression have been frequently detected in human benign tumours of mesenchymal origin. To better understand the role of HMGA2 overexpression in human tumorigenesis, we have generated transgenic mice carrying the HMGA2 gene under the transcriptional control of the cytomegalovirus promoter. High expression of the transgene was demonstrated in all the mouse tissues analysed, whereas no expression of the endogenous HMGA2 gene was detected in the same tissues from wild-type mice. In this study, two independent lines of transgenic mice have been generated. By 6 months of age, 85% of female animals of both transgenic lines developed pituitary adenomas secreting Prolactin and growth hormone. The transgenic males developed the same phenotype with a lower penetrance (40%) and a longer latency period (about 18 months). Therefore, these data demonstrate that the overexpression of HMGA2 leads to the onset of mixed growth hormone/Prolactin Cell pituitary adenomas. These transgenic mice may represent an important tool for the study of this kind of neoplasia.
