2024-03-28T13:52:20Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/73352022-10-11T13:37:06Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
Repisalud
author
Jiménez-García, Manuel-Pedro
author
Lucena-Cacace, Antonio
author
Robles-Frías, María-José
author
Ferrer, Irene
author
Narlik-Grassow, Maja
author
Blanco-Aparicio, Carmen
author
Carnero, Amancio
funder
Ministerio de Economía y Competitividad (España)
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Regional Government of Andalusia (España)
funder
Asociación Española Contra el Cáncer
2019-03-14T12:27:17Z
2019-03-14T12:27:17Z
2017-08-29
Oncotarget. 2017 ;8(35):58872-58886
1949-2553
http://hdl.handle.net/20.500.12105/7335
28938604
10.18632/oncotarget.19438
1949-2553
Oncotarget
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus. Furthermore, we observed a high degree of inflammatory infiltration in these tissues of transgenic mice accompanied by NFAT and mTOR activation and IL6 expression. Moreover, PIM1/2 were overexpressed in human breast, uterine and ovarian tumors, correlating with inflammatory features and stem cell markers. Our data suggest that PIM1/2 kinase overexpression provoke tissue alterations and a large IL6-dependent inflammatory response that may act synergistically during the process of tumorigenesis. The possible end-point is an increased percentage of cancer stem cells, which may be partly responsible for the therapy resistance found in tumors overexpressing PIM kinases.
eng
PIM kinases
Conditional transgenic mice
Mammary tumors
Oncogenesis
Reproductive system tumors
Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
journal article
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