Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein

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Tristetraprolin (TTP) is a RNA-binding protein that inhibits the expression of pro-inflammatory cytokines and invasiveness-associated genes. TTP levels are decreased in many different cancer types and it has been proposed that this protein could be used as a prognostic factor in breast cancer. Here,...

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Detalles Bibliográficos
Autores principales: Goddio, M. Victoria, Gattelli, Albana, Slomiansky, Victoria, Lacunza, Ezequiel, Gingerich, Timothy, Tocci, Johanna M., Facchinetti, María Marta, Curino, Alejandro Carlos, LaMarre, Jonathan, Abba, Martín Carlos, Kordon, Edith C.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
Materias:
Medicina
Ciencias Exactas
Tristetraprolin
Breast cancer
Mammary gland
Lactation
Prolactin
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/143148
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-143148
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
Ciencias Exactas
Tristetraprolin
Breast cancer
Mammary gland
Lactation
Prolactin
spellingShingle Medicina
Ciencias Exactas
Tristetraprolin
Breast cancer
Mammary gland
Lactation
Prolactin
Goddio, M. Victoria
Gattelli, Albana
Slomiansky, Victoria
Lacunza, Ezequiel
Gingerich, Timothy
Tocci, Johanna M.
Facchinetti, María Marta
Curino, Alejandro Carlos
LaMarre, Jonathan
Abba, Martín Carlos
Kordon, Edith C.
Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein
topic_facet Medicina
Ciencias Exactas
Tristetraprolin
Breast cancer
Mammary gland
Lactation
Prolactin
description Tristetraprolin (TTP) is a RNA-binding protein that inhibits the expression of pro-inflammatory cytokines and invasiveness-associated genes. TTP levels are decreased in many different cancer types and it has been proposed that this protein could be used as a prognostic factor in breast cancer. Here, using publicly available DNA microarray datasets, “serial analysis of gene expression” libraries and qRT-PCR analysis, we determined that TTP mRNA is present in normal breast cells and its levels are significantly decreased in all breast cancer subtypes. In addition, by immunostaining, we found that TTP expression is higher in normal breast tissue and benign lesions than in infiltrating carcinomas. Among these, lower grade tumors showed increased TTP expression compared to higher grade cancers. Therefore, these data indicate that TTP protein levels would provide a better negative correlation with breast cancer invasiveness than TTP transcript levels. In mice, we found that TTP mRNA and protein expression is also diminished in mammary tumors. Interestingly, a strong positive association of TTP expression and mammary differentiation was identified in normal and tumor cells. In fact, TTP expression is highly increased during lactation, showing good correlation with various mammary differentiation factors. TTP expression was also induced in mammary HC11 cells treated with lactogenic hormones, mainly by prolactin, through Stat5A activation. The effect of this hormone was highly dependent on mammary differentiation status, as prolactin was unable to elicit a similar response in proliferating or neoplastic mammary cells. In summary, these studies show that TTP expression is strongly linked to the mammary differentiation program in human and mice, suggesting that this protein might play specific and relevant roles in the normal physiology of the gland.
format Articulo
Articulo
author Goddio, M. Victoria
Gattelli, Albana
Slomiansky, Victoria
Lacunza, Ezequiel
Gingerich, Timothy
Tocci, Johanna M.
Facchinetti, María Marta
Curino, Alejandro Carlos
LaMarre, Jonathan
Abba, Martín Carlos
Kordon, Edith C.
author_facet Goddio, M. Victoria
Gattelli, Albana
Slomiansky, Victoria
Lacunza, Ezequiel
Gingerich, Timothy
Tocci, Johanna M.
Facchinetti, María Marta
Curino, Alejandro Carlos
LaMarre, Jonathan
Abba, Martín Carlos
Kordon, Edith C.
author_sort Goddio, M. Victoria
title Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein
title_short Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein
title_full Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein
title_fullStr Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein
title_full_unstemmed Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein
title_sort mammary differentiation induces expression of tristetraprolin, a tumor suppressor au-rich mrna-binding protein
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/143148
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