Involvement of Nuclear Receptor Coactivator SRC-1 in Estrogen-Dependent Cell Growth of MCF-7 Cells

Tai, Hitoshi; Kubota, Naoki; Kato, Shigeaki

doi:10.1006/bbrc.1999.1954

Cited by 43 publications

(29 citation statements)

References 40 publications

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“…src3-null mutant mice have been demonstrated to exhibit decreased development of mammary glands, suggesting that coactivators are critical for efficient proliferation and differentiation of mammary glands (38). Earlier studies also suggested that overexpression of ER coactivators such as SRC1and GRIP enables cell cycle progression (39,40). Even though these studies demonstrated that steroid coactivators enhance normal E 2 -mediated cell cycle progression, the mechanisms by which ER coregulators promote this progression remain elusive.…”

Section: Figmentioning

confidence: 99%

Functional Interactions between the Estrogen Receptor Coactivator PELP1/MNAR and Retinoblastoma Protein

Balasenthil

Vadlamudi

2003

Journal of Biological Chemistry

104

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PELP1 (proline-, glutamic acid-, and leucine-rich protein-1 (also referred to as MNAR, or modulator of nongenomic activity of estrogen receptor)), a recently identified novel coactivator of estrogen receptors, is widely expressed in a variety of 17␤-estradiol (E 2 )-responsive reproductive tissues and is developmentally regulated in mammary glands. pRb (retinoblastoma protein), a cell cycle switch protein, plays a fundamental role in the proliferation, development, and differentiation of eukaryotic cells. To study the putative function of PELP1, we established stable MCF-7 breast cancer cell lines overexpressing PELP1. PELP1 overexpression hypersensitized breast cancer cells to E 2 signaling, enhanced progression of breast cancer cells to S phase, and led to persistent hyperphosphorylation of pRb in an E 2 -dependent manner. Using phosphorylation site-specific pRb antibodies, we identified Ser-807/Ser-811 of pRb as a potential target site of PELP1. Interestingly, PELP1 was discovered to be physiologically associated with pRb and interacted via its C-terminal pocket domain, and PELP1/pRb interaction could be modulated by antiestrogen agents. Using mutant pRb cells, we demonstrated an essential role for PELP1/pRb interactions in the maximal coactivation functions of PELP1 using cyclin D1 as one of the targets. Taken together, these findings suggest that PELP1, a steroid coactivator, plays a permissive role in E 2 -mediated cell cycle progression, presumably via its regulatory interaction with the pRb pathway.The steroid hormone 17␤-estradiol (E 2 ) 1 plays an important role in controlling the expression of genes involved in a wide variety of biological processes, including development, homeostasis, and breast cancer progression (1, 2). The biological effects of estrogen are mediated by its binding to the structurally and functionally distinct estrogen receptors (ERs) ER␣ and ER␤. ER␣ is the major ER in mammary epithelium (3). Upon binding of E 2 to ER␣, the ligand-activated ER␣ translocates to the nucleus, binds to the 13-bp palindromic estrogen response element (ERE) in the target genes, and stimulates gene transcription, thus promoting cell proliferation (4). In addition to the genomic actions of ER, non-genomic functions are implicated via activation of intracellular signal transduction pathways involved in the regulation of cell proliferation (5-8).ER␣ comprises an N-terminal AF1 (activation function-1) domain, a DNA-binding domain, and a C-terminal ligandbinding region that contains an AF2 domain (9). The AF2 ligand-dependent activation function of ER␣ is located in the ligand-binding domain, whereas AF1 functions in a ligandindependent manner. AF1 and AF2 exhibit cell-type and promoter context specificity (10). Also, the transcription functions of ERs have been shown to be influenced by several coactivators, including SRC1 (steroid receptor coactivator-1), GRIP1, AIB1, CBP (cAMP response element-binding protein-binding protein), p300, PGC1, E6AP, PCAF (p300/CBP associating factor), and SNF2 (11-13). It is ge...

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Section: Figmentioning

confidence: 99%

Functional Interactions between the Estrogen Receptor Coactivator PELP1/MNAR and Retinoblastoma Protein

Balasenthil

Vadlamudi

2003

Journal of Biological Chemistry

104

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“…For example, increased expression of a member from the transcriptional mediator and intermediary factor proteins TIF2 and CREB-binding protein, and ER-a was observed in intraductal carcinomas of the breast [31], and enhanced expression of steroid receptor RNA activator was associated with mammary tumor progression [32]. Overexpression of SRC-1 potentates cell growth stimulated by E2 in breast cancer cells [33], whereas expression of high levels of SRC-1 in primary breast cancer is associated with a favorable response to tamoxifen in patients with recurrent disease [20]. Ampli®cation or overexpression of peroxisome proliferator±activated receptor binding protein gene is involved in 24±50% of primary breast cancers [15].…”

Section: DI Is Sc Cu Us Ss Si Io On Nmentioning

confidence: 99%

Expression ofRFG/ELE1?/ARA70 in normal and malignant prostatic epithelial cell cultures and lines: Regulation by methylation and sex steroids

Tekur¹,

Lau²,

Long³

et al. 2001

Mol. Carcinog.

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“…In vitro studies indicate that SRC-1 plays an important role in ER-mediated growth of breast cancer cells. Overexpression of SRC-1 potentiates E2-stimulated growth of MCF-7 breast cancer cells in accordance with an increase in the expression of estrogen-responsive genes (Tai et al, 2000). SRC-1 has also been reported to specifically promote breast cancer metastasis, possibly by promoting migration and invasion by enhancing PEA3 mediated transcriptional activation of Twist, a master regulator of metastasis (Qin et al, 2009).…”

Section: Expression and Functional Role Of Srcs In Breast Tissuementioning

confidence: 76%

Steroid Receptor Coactivators and Their Expression, Regulation and Functional Role in Endocrine Responsive and Resistant Breast Cancer

Moi¹,

Flågeng²,

Fenne³

et al. 2011

Breast Cancer - Carcinogenesis, Cell Growth and Signalling Pathways

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Involvement of Nuclear Receptor Coactivator SRC-1 in Estrogen-Dependent Cell Growth of MCF-7 Cells

Cited by 43 publications

References 40 publications

Functional Interactions between the Estrogen Receptor Coactivator PELP1/MNAR and Retinoblastoma Protein

Functional Interactions between the Estrogen Receptor Coactivator PELP1/MNAR and Retinoblastoma Protein

Expression ofRFG/ELE1?/ARA70 in normal and malignant prostatic epithelial cell cultures and lines: Regulation by methylation and sex steroids

Steroid Receptor Coactivators and Their Expression, Regulation and Functional Role in Endocrine Responsive and Resistant Breast Cancer

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