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Steroid receptor coactivator-3 and activator protein-1 coordinately regulate the transcription of components of the insulin-like growth factor/AKT signaling pathway.
Cancer Res. 2006 Nov 15; 66(22):11039-46.CR

Abstract

Steroid receptor coactivator (SRC)-3, also called amplified in breast cancer 1, is a member of the p160 nuclear receptor coactivator family involved in transcriptional regulation of target genes. SRC-3 is frequently amplified and/or overexpressed in hormone-sensitive and hormone-insensitive tumors. We reported previously that SRC-3 stimulated prostate cell growth in a hormone-independent manner through activation of AKT signaling pathway. However, the underlying mechanism remains undefined. Here, we exploited the mifepristone-induced SRC-3 LNCaP prostate cancer cell line generated in our laboratory to identify SRC-3-regulated genes by oligonucleotide microarray analysis. We found that SRC-3 up-regulates the expression of multiple genes in the insulin-like growth factor (IGF)/AKT signaling pathway that are involved in cell proliferation and survival. In contrast, knockdown of SRC-3 in PC3 (androgen receptor negative) prostate cancer cells and MCF-7 breast cancer cells reduces their expression. Similarly, in prostate glands of SRC-3 null mice, expressions of these components in the IGF/AKT signal pathway are also reduced. Chromatin immunoprecipitation assay revealed that SRC-3 was directly recruited to the promoters of these genes, indicating that they are direct targets of SRC-3. Interestingly, we showed that recruitment of SRC-3 to two target promoters, IRS-2 and IGF-I, requires transcription factor activator protein-1 (AP-1). Taken together, our results clearly show that SRC-3 and AP-1 can coordinately regulate the transcription of multiple components in the IGF/AKT pathway to ensure ligand-independent cell proliferation and survival of cancer cells.

Authors+Show Affiliations

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17108143

Citation

Yan, Jun, et al. "Steroid Receptor Coactivator-3 and Activator Protein-1 Coordinately Regulate the Transcription of Components of the Insulin-like Growth factor/AKT Signaling Pathway." Cancer Research, vol. 66, no. 22, 2006, pp. 11039-46.
Yan J, Yu CT, Ozen M, et al. Steroid receptor coactivator-3 and activator protein-1 coordinately regulate the transcription of components of the insulin-like growth factor/AKT signaling pathway. Cancer Res. 2006;66(22):11039-46.
Yan, J., Yu, C. T., Ozen, M., Ittmann, M., Tsai, S. Y., & Tsai, M. J. (2006). Steroid receptor coactivator-3 and activator protein-1 coordinately regulate the transcription of components of the insulin-like growth factor/AKT signaling pathway. Cancer Research, 66(22), 11039-46.
Yan J, et al. Steroid Receptor Coactivator-3 and Activator Protein-1 Coordinately Regulate the Transcription of Components of the Insulin-like Growth factor/AKT Signaling Pathway. Cancer Res. 2006 Nov 15;66(22):11039-46. PubMed PMID: 17108143.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Steroid receptor coactivator-3 and activator protein-1 coordinately regulate the transcription of components of the insulin-like growth factor/AKT signaling pathway. AU - Yan,Jun, AU - Yu,Cheng-Tai, AU - Ozen,Mustafa, AU - Ittmann,Michael, AU - Tsai,Sophia Y, AU - Tsai,Ming-Jer, PY - 2006/11/17/pubmed PY - 2006/12/15/medline PY - 2006/11/17/entrez SP - 11039 EP - 46 JF - Cancer research JO - Cancer Res VL - 66 IS - 22 N2 - Steroid receptor coactivator (SRC)-3, also called amplified in breast cancer 1, is a member of the p160 nuclear receptor coactivator family involved in transcriptional regulation of target genes. SRC-3 is frequently amplified and/or overexpressed in hormone-sensitive and hormone-insensitive tumors. We reported previously that SRC-3 stimulated prostate cell growth in a hormone-independent manner through activation of AKT signaling pathway. However, the underlying mechanism remains undefined. Here, we exploited the mifepristone-induced SRC-3 LNCaP prostate cancer cell line generated in our laboratory to identify SRC-3-regulated genes by oligonucleotide microarray analysis. We found that SRC-3 up-regulates the expression of multiple genes in the insulin-like growth factor (IGF)/AKT signaling pathway that are involved in cell proliferation and survival. In contrast, knockdown of SRC-3 in PC3 (androgen receptor negative) prostate cancer cells and MCF-7 breast cancer cells reduces their expression. Similarly, in prostate glands of SRC-3 null mice, expressions of these components in the IGF/AKT signal pathway are also reduced. Chromatin immunoprecipitation assay revealed that SRC-3 was directly recruited to the promoters of these genes, indicating that they are direct targets of SRC-3. Interestingly, we showed that recruitment of SRC-3 to two target promoters, IRS-2 and IGF-I, requires transcription factor activator protein-1 (AP-1). Taken together, our results clearly show that SRC-3 and AP-1 can coordinately regulate the transcription of multiple components in the IGF/AKT pathway to ensure ligand-independent cell proliferation and survival of cancer cells. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/17108143/Steroid_receptor_coactivator_3_and_activator_protein_1_coordinately_regulate_the_transcription_of_components_of_the_insulin_like_growth_factor/AKT_signaling_pathway_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17108143 DB - PRIME DP - Unbound Medicine ER -