Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-8-2
pubmed:abstractText
The mammalian testis-determining gene Sry and the related Sox genes define a family of transcriptional regulators widely expressed during embryogenesis. Tightly controlled temporal profiles of expression are a feature of the Sox gene family and may be required for initiation of a cascade of gene expression, yet the molecular mechanisms that control Sox gene expression are unknown. We now show that human SOX4 is expressed in the normal breast and in breast cancer cells. In these cells SOX4 is a progesterone-regulated gene, the expression of which is increased by progestins, leading to a marked increase in SOX-mediated transcriptional activity. Treatment of T-47D breast cancer cells with the synthetic progestin ORG 2058 directly increased SOX4 transcription, resulting in a 4-fold increase in SOX4 mRNA levels within 4 h of treatment. No effect of ORG 2058 was noted on other SOX genes measured, nor were other hormone-regulated HMG box proteins detected in this system, suggesting that the observed ability of progestin to increase SOX mRNA expression was confined to SOX4. The increase in SOX4 transcription was reflected in increased SOX4 protein expression, as progestin treatment of T-47D cells transfected with a SOX-responsive reporter resulted in a marked increase in reporter gene expression. Progesterone is essential for normal development and differentiation of the female reproductive system, plays an essential role in regulating growth and differentiation of the mammary gland and is required for opposing the proliferative effects of estrogen in specific cell types. The detection of SOX4 expression in the normal and malignant breast and the demonstration that SOX4 expression is under progesterone control suggests that changes in SOX4 gene expression may play a role in commitment to the differentiated phenotype in the normal and malignant mammary gland.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0952-5041
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
295-304
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Regulation of the expression and activity by progestins of a member of the SOX gene family of transcriptional modulators.
pubmed:affiliation
Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't