Effects of CREB3L1 on gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE51708 | GEO | 2013/10/26
SECONDARY ACCESSION(S): PRJNA224587
REPOSITORIES: GEO
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Project description:The unfolded protein response (UPR) is activated in response to hypoxia-induced stress such as in the tumor microenvironment. This study examined the role of CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the UPR, in breast cancer development and metastasis. Initial experiments identified the loss of CREB3L1 expression in metastatic breast cancer cell lines compared to low- or non-metastatic cell lines. When metastatic cells were transfected with CREB3L1 they demonstrated reduced invasion and migration in vitro, as well as a significantly decreased ability to survive under non-adherent or hypoxic conditions. Interestingly, in an in vivo rat mammary tumor model, CREB3L1 expressing cells not only failed to form metastases compared to CREB3L1 null cells but regression of the primary tumors was seen in 70% of the animals as a result of impaired angiogenesis. Microarray and ChIP on Chip analyses identified changes in the expression of many genes involved in cancer development and metastasis, including a decrease in those involved in angiogenesis. These data suggest that CREB3L1 plays an important role in suppressing tumorgenesis and loss of expression is required for the development of a metastatic phenotype. CREB3L1 is a member of the unfolded protein response family of proteins. CREB3L1 expression is lost from metastatic breast cancer cells. We wanted to determine the promoters of genes that CREB3L1 bound to. Idenification of promoters to which CREB3L1 is bound following ChIP with a HA antibody in MDA-MB-435 cells.
2013-10-30 | E-GEOD-51775 | biostudies-arrayexpress
Project description:The unfolded protein response (UPR) is activated in response to hypoxia-induced stress such as in the tumor microenvironment. This study examined the role of CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the UPR, in breast cancer development and metastasis. Initial experiments identified the loss of CREB3L1 expression in metastatic breast cancer cell lines compared to low- or non-metastatic cell lines. When metastatic cells were transfected with CREB3L1 they demonstrated reduced invasion and migration in vitro, as well as a significantly decreased ability to survive under non-adherent or hypoxic conditions. Interestingly, in an in vivo rat mammary tumor model, CREB3L1 expressing cells not only failed to form metastases compared to CREB3L1 null cells but regression of the primary tumors was seen in 70% of the animals as a result of impaired angiogenesis. Microarray and ChIP on Chip analyses identified changes in the expression of many genes involved in cancer development and metastasis, including a decrease in those involved in angiogenesis. These data suggest that CREB3L1 plays an important role in suppressing tumorgenesis and loss of expression is required for the development of a metastatic phenotype. CREB3L1 is a member of the unfolded protein response family of proteins. CREB3L1 expression is lost from metastatic breast cancer cells. We wanted to determine the promoters of genes that CREB3L1 bound to. Idenification of promoters to which CREB3L1 is bound following ChIP with a HA antibody or control.
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Project description:The unfolded protein response (UPR) is activated in response to hypoxia-induced stress such as in the tumor microenvironment. This study examined the role of CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the UPR, in breast cancer development and metastasis. Initial experiments identified the loss of CREB3L1 expression in metastatic breast cancer cell lines compared to low- or non-metastatic cell lines. When metastatic cells were transfected with CREB3L1 they demonstrated reduced invasion and migration in vitro, as well as a significantly decreased ability to survive under non-adherent or hypoxic conditions. Interestingly, in an in vivo rat mammary tumor model, CREB3L1 expressing cells not only failed to form metastases compared to CREB3L1 null cells but regression of the primary tumors was seen in 70% of the animals as a result of impaired angiogenesis. Microarray and ChIP on Chip analyses identified changes in the expression of many genes involved in cancer development and metastasis, including a decrease in those involved in angiogenesis. These data suggest that CREB3L1 plays an important role in suppressing tumorgenesis and loss of expression is required for the development of a metastatic phenotype. CREB3L1 is a member of the unfolded protein response family of proteins. CREB3L1 expression is lost from metastatic breast cancer cells. We wanted to determine the effctes CREB3L1 expression had on gene expression. RNA was extracted from LN4D6 rats cells that were either untransfected or transfected with CREB3L1, changes in gene expression following transfection of CREB3l1 were then determined by hybridisation on Affymetrics microarrays.
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Project description:The unfolded protein response (UPR) is activated in response to hypoxia-induced stress such as in the tumor microenvironment. This study examined the role of CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the UPR, in breast cancer development and metastasis. Initial experiments identified the loss of CREB3L1 expression in metastatic breast cancer cell lines compared to low- or non-metastatic cell lines. When metastatic cells were transfected with CREB3L1 they demonstrated reduced invasion and migration in vitro, as well as a significantly decreased ability to survive under non-adherent or hypoxic conditions. Interestingly, in an in vivo rat mammary tumor model, CREB3L1 expressing cells not only failed to form metastases compared to CREB3L1 null cells but regression of the primary tumors was seen in 70% of the animals as a result of impaired angiogenesis. Microarray and ChIP on Chip analyses identified changes in the expression of many genes involved in cancer development and metastasis, including a decrease in those involved in angiogenesis. These data suggest that CREB3L1 plays an important role in suppressing tumorgenesis and loss of expression is required for the development of a metastatic phenotype. CREB3L1 is a member of the unfolded protein response family of proteins. CREB3L1 expression is lost from metastatic breast cancer cells. We wanted to determine the promoters of genes that CREB3L1 bound to.
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Project description:A data-entrained computational model for
testing the regulatory logic of the vertebrate unfolded protein
response
This model is described in the article:
A data-entrained
computational model for testing the regulatory logic of the
vertebrate unfolded protein response.
Diedrichs DR, Gomez JA, Huang CS,
Rutkowski DT, Curtu R.
Mol. Biol. Cell 2018 Apr; :
mbcE17090565
Abstract:
The vertebrate unfolded protein response (UPR) is
characterized by multiple interacting nodes among its three
pathways, yet the logic underlying this regulatory complexity
is unclear. To begin to address this issue, we created a
computational model of the vertebrate UPR that was entrained
upon and then validated against experimental data. As part of
this validation, the model successfully predicted the
phenotypes of cells with lesions in UPR signaling, including a
surprising and previously unreported differential role for the
eIF2? phosphatase GADD34 in exacerbating severe stress but
ameliorating mild stress. We then used the model to test the
functional importance of a feed-forward circuit within the
PERK/CHOP axis, and of cross-regulatory control of BiP and CHOP
expression. We found that the wiring structure of the UPR
appears to balance the ability of the response to remain
sensitive to ER stress yet also to be rapidly deactivated by
improved protein folding conditions. This model should serve as
a valuable resource for further exploring the regulatory logic
of the UPR.
This model is hosted on
BioModels Database
and identified by:
MODEL1803300000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000703 | BioModels