Identification of an AP1-ZFP36 Regulatory Network Associated with Breast Cancer Prognosis
It has been established that ZFP36 (also known as Tristetraprolin or TTP) promotes mRNA degradation of proteins involved in inflammation, proliferation and tumor invasiveness. In mammary epithelial cells ZFP36 expression is induced by STAT5 activation during lactogenesis, while in breast cancer ZFP3...
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Published in | Journal of mammary gland biology and neoplasia Vol. 25; no. 2; pp. 163 - 172 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.06.2020
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | It has been established that ZFP36 (also known as Tristetraprolin or TTP) promotes mRNA degradation of proteins involved in inflammation, proliferation and tumor invasiveness. In mammary epithelial cells
ZFP36
expression is induced by STAT5 activation during lactogenesis, while in breast cancer
ZFP36
expression is associated with lower grade and better prognosis. Here, we show that the AP-1 transcription factor components, i.e.
JUN, JUNB, FOS, FOSB
, in addition to
DUSP1, EGR1, NR4A1
,
IER2
and
BTG2
, behave as a conserved co-regulated group of genes whose expression is associated to
ZFP36
in cancer cells. In fact, a significant down-modulation of this gene network is observed in breast, liver, lung, kidney, and thyroid carcinomas compared to their normal counterparts. In breast cancer, the normal-like and Luminal A, show the highest expression of the
ZFP36
gene network among the other intrinsic subtypes and patients with low expression of these genes display poor prognosis. It is also proposed that AP-1 regulates
ZFP36
expression through responsive elements detected in the promoter region of this gene. Culture assays show that AP-1 activity induces
ZFP36
expression in mammary cells in response to prolactin (PRL) treatment thorough ERK1/2 activation. These results suggest that
JUN, JUNB, FOS and FOSB
are not only co-expressed, but would also play a relevant role in regulating
ZFP36 expression
in mammary epithelial cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1083-3021 1573-7039 |
DOI: | 10.1007/s10911-020-09448-1 |