Immunological and Functional Characterization of RhoGDI3 and Its Molecular Targets RhoG and RhoB in Human Pancreatic Cancerous and Normal Cells
Por:
Piedad de Leon-Bautista, Mercedes, del Carmen Cardenas-Aguayo, Maria, Casique-Aguirre, Diana, Almaraz-Salinas, Manuel, Parraguirre-Martinez, Sara, Olivo-Diaz, Angelica, del Rocio Thompson-Bonilla, Maria, Vargas, Miguel
Publicada:
10 nov 2016
Resumen:
RhoGDI proteins have been implicated in several human cancers; changes
in their expression levels have shown pro-or anti-tumorigenic effects.
Pancreatic Ductal Adenocarcinoma (PDAC) is a complex pathology, with
poor prognosis, and most patients die shortly after diagnosis. Efforts
have been focused on understanding the role of RhoGDI's in PDAC,
specially, RhoGDI1 and RhoGDI2. However, the role of RhoGDI3 has not
been studied in relation to cancer or to PDAC. Here, we characterized
the expression and functionality of RhoGDI3 and its target GTPases, RhoG
and RhoB in pancreatic cell lines from both normal pancreatic tissue and
tissue in late stages of PDAC, and compared them to human biopsies.
Through immunofluorescences, pulldown assays and subcellular
fractionation, we found a reduction in RhoGDI3 expression in the late
stages of PDAC, and this reduction correlates with tumor progression and
aggressiveness. Despite the reduction in the expression of RhoGDI3 in
PDAC, we found that RhoB was underexpressed while RhoG was
overexpressed, suggesting that cancerous cells preserve their capacity
to activate this pathway, thus these cells may be more eager to response
to the stimuli needed to proliferate and become invasive unlike normal
cells. Surprisingly, we found nuclear localization of RhoGDI3 in non
-cancerous pancreatic cell line and normal pancreatic tissue biopsies,
which could open the possibility of novel nuclear functions for this
protein, impacting gene expression regulation and cellular homeostasis.
Filiaciones:
Piedad de Leon-Bautista, Mercedes:
Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biomed Mol, Ave Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico
del Carmen Cardenas-Aguayo, Maria:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Ave Univ 3000, Delegacion Coyoacan 04510, Mexico
Casique-Aguirre, Diana:
Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biomed Mol, Ave Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico
Almaraz-Salinas, Manuel:
Inst Tecnol Milpa Alta, Fac Bioquim, Independencia 36, Mexico City 12300, DF, Mexico
Parraguirre-Martinez, Sara:
Hosp Gen Doctor Manuel Gea Gonzalez, Dept Anat Patol, Av Calzada Tlalpan 4800,Sect 16, Mexico City 14080, DF, Mexico
Olivo-Diaz, Angelica:
Hosp Doctor Manuel Gea Gonzalez, Dept Biol Mol & Histocompatibilidad, Av Calzada Tlalpan 4800,Sect 16, Mexico City 14080, DF, Mexico
del Rocio Thompson-Bonilla, Maria:
Hosp 1 Octubre, ISSSTE, Lab Med Genom, Invest Biomed Traslac, Av Inst Politecn Nacl 1669, Mexico City 07760, DF, Mexico
Vargas, Miguel:
Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biomed Mol, Ave Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico
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