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EPAS-1 mediates SP-1-dependent FBI-1 expression and regulates tumor cell survival and proliferation.

Wang X, Cao P, Li Z, Wu D, Wang X, Liang G - Int J Mol Sci (2014)

Bottom Line: In this work, we aimed to study the role that EPAS-1 plays in regulating FBI-1.We use the fact that specificity protein-1 (SP-1) is one of the crucial transcription factors of FBI-1, and that SP-1 can interact with the endothelial pas domain protein-1 (EPAS-1) for the induction of hypoxia related genes.The study showed that EPAS-1 plays an indispensible role in SP-1 transcription factor-mediated FBI-1 induction, and participated in tumor cell survival and proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Institute of Neurology, General Hospital of Shenyang Military Area Command, Shenyang 110016, China. xiaogangwangzy@163.com.

ABSTRACT
Factor binding IST-1 (FBI-1) plays an important role in oncogenic transformation and tumorigenesis. As FBI-1 is over-expressed in multiple human cancers, the regulation of itself would provide new effective options for cancer intervention. In this work, we aimed to study the role that EPAS-1 plays in regulating FBI-1. We use the fact that specificity protein-1 (SP-1) is one of the crucial transcription factors of FBI-1, and that SP-1 can interact with the endothelial pas domain protein-1 (EPAS-1) for the induction of hypoxia related genes. The study showed that EPAS-1 plays an indispensible role in SP-1 transcription factor-mediated FBI-1 induction, and participated in tumor cell survival and proliferation. Thus, EPAS-1 could be a novel target for cancer therapeutics.

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Related in: MedlinePlus

EPAS-1 specifically regulates SP-1-mediated FBI-1 expression. (A) EPAS-1 significantly induced the luciferase activities of all the SP-1 binding sites on FBI-1 promoter. Data points were determined in triplicate and shown with the mean ± SD (* p < 0.05, t-test). The luciferase reporter gene vectors were described in reference [18]; (B) EPAS-1 could not significantly induce the luciferase activities of the non-SP-1 binding sites on FBI-1 promoter. Data points were determined in triplicate and showed with the mean ± SD (* p < 0.05, t-test). The luciferase reporter gene vectors were described in reference [18].
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ijms-15-15689-f004: EPAS-1 specifically regulates SP-1-mediated FBI-1 expression. (A) EPAS-1 significantly induced the luciferase activities of all the SP-1 binding sites on FBI-1 promoter. Data points were determined in triplicate and shown with the mean ± SD (* p < 0.05, t-test). The luciferase reporter gene vectors were described in reference [18]; (B) EPAS-1 could not significantly induce the luciferase activities of the non-SP-1 binding sites on FBI-1 promoter. Data points were determined in triplicate and showed with the mean ± SD (* p < 0.05, t-test). The luciferase reporter gene vectors were described in reference [18].

Mentions: There are several responsible elements for different transcription factors in FBI-1 promoter region [18]. We analyzed the previous report about the promoter region of FBI-1 gene, cloned 10 SP-1 binding sites and other sites which contain the regulatory elements such as NEG-U and NEG-D or be responsible to other transcription factors such as p53, GATA-1 and AP-2. The gene reporter assay showed that EPAS-1 specifically increased the luciferase activities of the full-length promoter (Normal) and all the SP-1 binding sites vectors (Figure 4A). On the other hand, EPAS-1 could not significantly alter the activities of other reporter gene vectors containing the non-SP-1-targeting sites described above (Figure 4B). Both results indicated that EPAS-1 specifically participates in SP-1-mediated FBI-1 expression.


EPAS-1 mediates SP-1-dependent FBI-1 expression and regulates tumor cell survival and proliferation.

Wang X, Cao P, Li Z, Wu D, Wang X, Liang G - Int J Mol Sci (2014)

EPAS-1 specifically regulates SP-1-mediated FBI-1 expression. (A) EPAS-1 significantly induced the luciferase activities of all the SP-1 binding sites on FBI-1 promoter. Data points were determined in triplicate and shown with the mean ± SD (* p < 0.05, t-test). The luciferase reporter gene vectors were described in reference [18]; (B) EPAS-1 could not significantly induce the luciferase activities of the non-SP-1 binding sites on FBI-1 promoter. Data points were determined in triplicate and showed with the mean ± SD (* p < 0.05, t-test). The luciferase reporter gene vectors were described in reference [18].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4200855&req=5

ijms-15-15689-f004: EPAS-1 specifically regulates SP-1-mediated FBI-1 expression. (A) EPAS-1 significantly induced the luciferase activities of all the SP-1 binding sites on FBI-1 promoter. Data points were determined in triplicate and shown with the mean ± SD (* p < 0.05, t-test). The luciferase reporter gene vectors were described in reference [18]; (B) EPAS-1 could not significantly induce the luciferase activities of the non-SP-1 binding sites on FBI-1 promoter. Data points were determined in triplicate and showed with the mean ± SD (* p < 0.05, t-test). The luciferase reporter gene vectors were described in reference [18].
Mentions: There are several responsible elements for different transcription factors in FBI-1 promoter region [18]. We analyzed the previous report about the promoter region of FBI-1 gene, cloned 10 SP-1 binding sites and other sites which contain the regulatory elements such as NEG-U and NEG-D or be responsible to other transcription factors such as p53, GATA-1 and AP-2. The gene reporter assay showed that EPAS-1 specifically increased the luciferase activities of the full-length promoter (Normal) and all the SP-1 binding sites vectors (Figure 4A). On the other hand, EPAS-1 could not significantly alter the activities of other reporter gene vectors containing the non-SP-1-targeting sites described above (Figure 4B). Both results indicated that EPAS-1 specifically participates in SP-1-mediated FBI-1 expression.

Bottom Line: In this work, we aimed to study the role that EPAS-1 plays in regulating FBI-1.We use the fact that specificity protein-1 (SP-1) is one of the crucial transcription factors of FBI-1, and that SP-1 can interact with the endothelial pas domain protein-1 (EPAS-1) for the induction of hypoxia related genes.The study showed that EPAS-1 plays an indispensible role in SP-1 transcription factor-mediated FBI-1 induction, and participated in tumor cell survival and proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Institute of Neurology, General Hospital of Shenyang Military Area Command, Shenyang 110016, China. xiaogangwangzy@163.com.

ABSTRACT
Factor binding IST-1 (FBI-1) plays an important role in oncogenic transformation and tumorigenesis. As FBI-1 is over-expressed in multiple human cancers, the regulation of itself would provide new effective options for cancer intervention. In this work, we aimed to study the role that EPAS-1 plays in regulating FBI-1. We use the fact that specificity protein-1 (SP-1) is one of the crucial transcription factors of FBI-1, and that SP-1 can interact with the endothelial pas domain protein-1 (EPAS-1) for the induction of hypoxia related genes. The study showed that EPAS-1 plays an indispensible role in SP-1 transcription factor-mediated FBI-1 induction, and participated in tumor cell survival and proliferation. Thus, EPAS-1 could be a novel target for cancer therapeutics.

Show MeSH
Related in: MedlinePlus