Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P04155 (
pS2
)
1,234
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
ICB-1
chromosome 1 open reading frame 38
(
C1orf38
) is a human gene initially described by our group to be involved in differentiation processes of cancer cells. Recently, we have reported
ICB-1
as a novel estrogen target gene and identified an estrogen response element in its promoter. In this study, we examined the role of
ICB-1
in regulation of proliferation of breast and ovarian cancer cells. We knocked down its expression in estrogen-dependent MCF-7 breast cancer cells and hormone-unresponsive SK-OV-3 ovarian cancer cells by stable transfection with a specific shRNA plasmid followed by G-418 selection. Knockdown of
ICB-1
enabled a considerable estrogen response of SK-OV-3 cells in terms of proliferation. This transformation of SK-OV-3 cells into an estrogen-responsive phenotype was accompanied by upregulation of estrogen receptor alpha (ERalpha) expression and a significant decrease of ERbeta expression on the mRNA level. Expression of ERalpha-dependent genes progesterone receptor,
pS2
, fibulin 1c, and c-fos was elevated in SK-OV-3 cells stably expressing
ICB-1
shRNA. In MCF-7 cells,
ICB-1
knockdown exerted similar effects on gene expression, supporting a general role of
ICB-1
in estrogen responsiveness. Our data suggest that differentiation-associated gene
ICB-1
might exert antagonistic actions on cellular estrogen response, which can result in inhibition of estradiol-triggered proliferation. The molecular mechanisms mediating this inhibitory effect of
ICB-1
on estrogen signaling are suggested to be limitation of ERalpha transcript levels but sustaining high levels of ERbeta, reducing both activation of ERalpha target genes and cellular proliferation. The identification of
ICB-1
as a new player in endocrine-related cancer encourages further studies on the significance of this gene in cancer development and therapy.
...
PMID:Knockdown of ICB-1 gene enhanced estrogen responsiveness of ovarian and breast cancer cells. 1994 13
