Involvement of Ets‐related proteins in hormone‐independent mammary cell‐specific gene expression

Welte, Thomas; Garimorth, Katja; Philipp, Sonja; Jennewein, Patricia; Huck, Carmen; Cato, Andrew C. B.; Doppler, Wolfgang

doi:10.1111/j.1432-1033.1994.tb19078.x

Cited by 34 publications

(21 citation statements)

References 42 publications

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“…The expression pattern of ELF5 matches closely that of erbB2, with the exception that ELF5 does not appear to be expressed in the intestine. ETS factors have also been implicated in the regulation of other genes important to epithelial cell function and/or transformation, including c-met (Gambarotta et al, 1996), transforming growth factor-b type II receptor (TGF-b RII) (Choi et al, 1998), transglutaminase-3 (Lee et al, 1996, SPRR2A (Fischer et al, 1996) and whey acidic protein (WAP) (Welte et al, 1994), but identi®cation of the speci®c ETS factors involved has not yet been made.…”

Section: Discussionmentioning

confidence: 99%

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

Zhou

Tymms

et al. 1998

Oncogene

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The ETS transcription factors are a large family implicated in the control of cellular proliferation and tumorigenesis. In addition, chromosomal translocations involving ETS family members are associated with a range of di erent human cancers. Given the extensive involvement of ETS factors in tumorigenesis, it becomes important to identify any additional ETS genes that may also play oncogenic roles. We identify a novel gene, ELF5, that appears to belong to the ELF (E74-likefactor) subfamily of the ETS transcription factor family, based upon similarity within the`ETS domain'. ELF5 displays a similar, but more restricted, expression pattern to that of the newly isolated epithelium-speci®c ETS gene, ELF3. Unlike most other ETS family members, ELF5 is not expressed in hematopoietic compartments, but is restricted to organs such as lung, stomach, kidney, prostate, bladder and mammary gland. ELF5 is localized to human chromosome 11p13 ± 15, a region that frequently undergoes loss of heterozygosity (LOH) in several types of carcinoma, including those of breast, kidney and prostate. We ®nd that ELF5 expression is not detectable in a number of carcinoma cell lines, some of which display loss or rearrangement of an ELF5 allele. Similar to other ETS family members, ELF5 displays speci®c binding to DNA sequences containing a GGAA-core. In addition, ELF5 is able to transactivate through these ETS sequences, present upstream from a minimal promoter. Our data suggest that ELF5 may play roles in mammary, lung, prostate and/or kidney function, and possibly also in tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

Zhou

Tymms

et al. 1998

Oncogene

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“…Electromobility shift assays were performed on a 4% polyacrylamide gel in 0.25 ϫ TBE electrophoresis buffer. Binding reactions were as described (27). GR-DBD expressed in Escherichia coli was purified as described (28) and used for binding reactions in a buffer containing 10 mM Hepes, pH 7.5, 2.5 mM MgCl 2 , 10% glycerol (w/v), 50 mM KCl, 0.1 mM EDTA, 1 mM dithiothreitol, 50 ng of poly(dI-dC).…”

Section: Methodsmentioning

confidence: 99%

Promoter-dependent Synergy between Glucocorticoid Receptor and Stat5 in the Activation of β-Casein Gene Transcription

Lechner¹,

Welte²,

Tomasi³

et al. 1997

Journal of Biological Chemistry

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118

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“…Some of the experiments with COS-7 cells were also performed in 24-well dishes and 0.5 ϫ 10 5 to 1 ϫ 10 5 cells per well. The next day, transfections were carried out using the calcium phosphate coprecipitation technique as described previously (35). The total amount of DNA transfected was adjusted to the area of the culture dishes used; it was 3.3 or 0.83 g of DNA per well for a 6-well dish or 24-well dish, respectively.…”

Section: Plasmidsmentioning

confidence: 99%

Expression Level-Dependent Contribution of Glucocorticoid Receptor Domains for Functional Interaction with STAT5

Doppler¹,

Windegger²,

Soratroi³

et al. 2001

Molecular and Cellular Biology

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The action of the glucocorticoid receptor (GR) on ␤-casein gene transcription serves as a well-studied example of a case where the action of the GR is dependent on the activity of another transcription factor, STAT5. We have investigated the domain-requirement of the GR for this synergistic response in transfection experiments employing GR mutants and CV-1 or COS-7 cells. The results were influenced by the expression levels of the GR constructs. At low expression, STAT5-dependent transactivation by mutants of the GR DNA binding domain or N-terminal transactivation domain was impaired and the antiglucocorticoid RU486 exhibited a weak agonistic activity. When the N-terminal region of the GR was exchanged with the respective domain of the progesterone receptor, STAT5-dependent transactivation was reduced at low and high expression levels. Only at high expression levels did the GR exhibit the properties of a coactivator and enhanced STAT5 activity in the absence of a functional DNA binding domain and of GR binding sites in the proximal region of the ␤-casein gene promoter. Furthermore, at high GR expression levels RU486 was nearly as efficient as dexamethasone in activating transcription via the STAT5 dependent ␤-casein gene promoter. The results reconcile the controversial issue regarding the DNA binding-independent action of the GR together with STAT5 and provide evidence that the mode of action of the GR depends not only on the type of the particular promoter at which it acts but also on the concentration of the GR. GR DNA binding function appears to be mandatory for ␤-casein gene expression in mammary epithelial cells, since the promoter function is completely dependent on the integrity of GR binding sites in the promoter.Modulation of gene expression by the glucocorticoid receptor (GR) involves a combination of several mechanisms such as modulation of chromatin structure (5, 27); binding to specific DNA response elements (24); interaction with sequence-specific transcription factors, coactivators, and corepressors; and ligand-dependent alterations in the balance of corepressors and coactivators bound to the receptor (20). The actual type of mechanism employed by the receptor strongly depends on the genes that are regulated and on the cellular context. There is a differential requirement for domains in the GR, depending on the prevalent mechanism utilized by the receptor. For instance, a specific subset of GR-regulated genes is affected in transgenic mice in which the wild-type GR is replaced by a mutant defective in dimerization (26). Since this mutant is strongly impaired in binding to palindromic canonical glucocorticoid response elements (GREs) (7), it can no longer regulate genes that contain functional GREs. Consistent with the observation that in most cases the binding of the GR to DNA is a prerequisite for transactivation but not for transrepression, transgenic mice expressing the dimerization mutant predominantly exhibit a defect in the expression of genes induced by glucocorticoids.One of the exception...

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Involvement of Ets‐related proteins in hormone‐independent mammary cell‐specific gene expression

Cited by 34 publications

References 42 publications

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

Promoter-dependent Synergy between Glucocorticoid Receptor and Stat5 in the Activation of β-Casein Gene Transcription

Expression Level-Dependent Contribution of Glucocorticoid Receptor Domains for Functional Interaction with STAT5

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