Regulation of the expression and activity by progestins of a member of the SOX gene family of transcriptional modulators. (1/146)

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.  (+info)

Expression and hormonal regulation of the Sox4 gene in mouse female reproductive tissues. (2/146)

The SOX genes define a family of transcriptional regulators whose diverse patterns and tightly controlled temporal profiles of expression suggest that they play key roles in determination of cell fate during development. One of the family members, Sox4, is expressed in the gonads of adult mice, but expression in the reproductive tissues has not been studied. As previous studies in this laboratory had shown that the SOX4 gene was regulated by ovarian hormones in breast cancer cells, murine Sox4 expression was analyzed in the reproductive tissues of mice by Northern blot analysis and ribonuclease protection assays. Sox4 mRNA expression was detected in the uterus and, at a lower level, in the mammary glands of pubertal and adult mice. Expression was modulated in the uterus of intact mice at various stages of the estrous cycle and was reduced by estradiol treatment of ovariectomized mice. Progesterone treatment partially reversed the estradiol effect. Although no modulation of Sox4 expression in the mammary glands was detected by Northern blot analysis, further evaluation of Sox4 protein expression at a cellular level is required. No modulation of Sox4 levels was observed in the thymus. The results presented here suggest that expression of the Sox4 gene is under ovarian hormone control in the uterus and implicate Sox4 in the complex effects controlled by ovarian hormones in the female reproductive system.  (+info)

Expression patterns of zebrafish sox11A, sox11B and sox21. (3/146)

We have cloned three sox genes in zebrafish (Danio rerio), one related to human and chicken SOX21, and two related to mammalian and chicken Sox-11. Zebrafish sox21, sox11A and sox11B transcripts are accumulated in the egg, are present in all cells until gastrulation and become restricted later to the developing central nervous system (CNS); expression in adults is undetectable. sox21 is expressed in the forebrain, midbrain and hindbrain, but maximally at the midbrain-hindbrain junction; sox11A,B have a widespread and dynamic expression in the CNS, but in contrast to sox21 are absent at the midbrain-hindbrain boundary.  (+info)

Human SOX11, an upregulated gene during the neural differentiation, has a long 3' untranslated region. (4/146)

To obtain essential genes for neuronal development, we have performed a molecular indexing method using a human teratocarcinoma cell line, NTera-2. We isolated a cDNA fragment, designated B18, as an upregulated gene during the neural differentiation. From the complete cDNA sequence of B18 it was revealed that this cDNA was the human SOX11 gene. While a previous report has determined only a approximately 2 kb of the SOX11 cDNA including the entire open reading frame, our full length cDNA was 8743 bp possessing a long 3' untranslated region. Human SOX11 cDNA was mapped to chromosome region 2p25.3 between markers AFMA070WC9 and WI-1412 by radiation hybrid mapping.  (+info)

Expression of sox11 gene duplicates in zebrafish suggests the reciprocal loss of ancestral gene expression patterns in development. (5/146)

To investigate the role of sox genes in vertebrate development, we have isolated sox11 from zebrafish (Danio rerio). Two distinct classes of sox11-related cDNAs were identified, sox11a and sox11b. The predicted protein sequences shared 75% identity. In a gene phylogeny, both sox11a and sox11b cluster with human, mouse, chick, and Xenopus Sox11, indicating that zebrafish, like Xenopus, has two orthologues of tetrapod Sox11. The work reported here investigates the evolutionary origin of these two gene duplicates and the consequences of their duplication for development. The sox11a and sox11b genes map to linkage groups 17 and 20, respectively, together with other loci whose orthologues are syntenic with human SOX11, suggesting that during the fish lineage, a large chromosome region sharing conserved syntenies with mammals has become duplicated. Studies in mouse and chick have shown that Sox11 is expressed in the central nervous system during development. Expression patterns of zebrafish sox11a and sox11b confirm that they are expressed in the developing nervous system, including the forebrain, midbrain, hindbrain, eyes, and ears from an early stage. Other sites of expression include the fin buds and somites. The two sox genes, sox11a and sox11b, are expressed in both overlapping and distinct sites. Their expression patterns suggest that sox11a and sox11b may share the developmental domains of the single Sox11 gene present in mouse and chick. For example, zebrafish sox11a is expressed in the anterior somites, and zebrafish sox11b is expressed in the posterior somites, but the single Sox11 gene of mouse is expressed in all the somites. Thus, the zebrafish duplicate genes appear to have reciprocally lost expression domains present in the sox11 gene of the last common ancestor of tetrapods and zebrafish. This splitting of the roles of Sox11 between two paralogues suggests that regulatory elements governing the expression of the sox11 gene in the common ancestor of zebrafish and tetrapods may have been reciprocally mutated in the zebrafish gene duplicates. This is consistent with duplicate gene evolution via a duplication-degeneration-complementation process.  (+info)

Delineation of the 6p22 amplification unit in urinary bladder carcinoma cell lines. (6/146)

Eight cell lines from transitional cell carcinoma of the urinary bladder were analyzed by comparative genomic hybridization. All tumor lines exhibited frequent chromosome gains (11.5/cell line) and losses (8.4/cell line). In six cell lines, gain of chromosome 5p was associated with gains of 6p and 20q. In five of these cell lines, amplification of parts of 6p was observed. Cytogenetic investigation combined with fluorescence in situ hybridization analysis revealed typical marker chromosomes with homogeneously staining regions (HSRs) containing material from 6p. By hybridizing individual yeast artificial chromosome probes from a chromosome 6p contig to these HSRs, a contig of three yeast artificial chromosomes common to all 6p HSRs was identified that spans less than 2 Mb. The genes SOX4 and PRL were shown to map to this region and to be coamplified in the cell lines. However, SOX4 was not overexpressed in any cell line and PRL was not expressed at all. Thus, the presumptive 6p oncogene remains to be conclusively identified.  (+info)

Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein. (7/146)

Cytokine receptors consist of multiple subunits, which are often shared between different receptors, resulting in the functional redundancy sometimes observed between cytokines. The interleukin 5 (IL-5) receptor consists of an IL-5-specific alpha-subunit (IL-5Ralpha) and a signal-transducing beta-subunit (betac) shared with the IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors. In this study, we sought to find a role for the cytoplasmic domain of IL-5Ralpha. We show that syntenin, a protein containing PSD-95/Discs large/zO-1 (PDZ) domains, associates with the cytoplasmic tail of the IL-5Ralpha. Syntenin was found to directly associate with the transcription factor Sox4. Association of syntenin with IL-5Ralpha was required for IL-5-mediated activation of Sox4. These studies identify a mechanism of transcriptional activation by cytokine-specific receptor subunits.  (+info)

Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by prostaglandin (PG)A(2) and delta(12)-PGJ(2). (8/146)

We reported earlier that expression of Sox-4 was found to be elevated during prostaglandin (PG) A(2) and delta(12)-PGJ(2) induced apoptosis in human hepatocarcinoma Hep3B cells. In this study, the role of Sox-4 was examined using human Hep3B and HepG2 cell lines. Sox-4 induction by several apoptotic inducer such as A23187 (Ca(2+) ionophore) and etoposide (topoisomerase II inhibitor) and Sox-4 transfection into the cells were able to induce apoptosis as observed by the cellular DNA fragmentation. Antisense oligonucleotide of Sox-4 inhibited the induction of Sox-4 expression and blocked the formation of DNA fragmentation by PGA(2) and delta(12)-PGJ(2) in Hep3B and HepG2 cells. Sox-4-induced apoptosis was accompanied with caspase-1 activation indicating that caspase cascade was involved in this apoptotic pathway. These results indicate that Sox-4 is involved in Hep3B and HepG2 cells apoptosis as an important apoptotic mediator.  (+info)

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