Activation of the unliganded estrogen receptor by prolactin in breast cancer cells

González, Lorena; Zambrano, Alberto; Lazaro-Trueba, Iciar; López, Elena; González, Janneth; Martı́n-Pérez, Jorge; Aranda, Ana

doi:10.1038/onc.2008.473

Cited by 56 publications

(45 citation statements)

References 55 publications

(79 reference statements)

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“…Additionally, the cooperative effects of these three hormones may occur in part due to mutual induction of each other's receptors. While Prl upregulates PR mRNA in the mammary gland (Ormandy et al, 1997) and activates ERα in T47D cells (Gonzalez et al, 2009), PrlR mRNA is induced by P in T47D cells (Tseng and Zhu, 1998) and by E in MCF7 cells (Dong et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Progesterone induces expression of the prolactin receptor gene through cooperative action of Sp1 and C/EBP

Goldhar

Duan

Ginsburg

et al. 2011

Molecular and Cellular Endocrinology

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Prolactin (Prl) and progesterone (P) cooperate synergistically during mammary gland development and tumorigenesis. We hypothesized that one mechanism for these effects may be through mutual induction of receptors (R). EpH4 mouse mammary epithelial cells stably transfected with PR-A express elevated levels of PrlR mRNA and protein compared to control EpH4 cells that lack the PR. Likewise, T47D human breast cancer cells treated with P overexpress the PrlR and activate PrlR promoter III. PrlR promoter III does not contain a classical P response element but contains several binding sites for transcription proteins, including C/EBP, Sp1 and AP1, which may also interact with the PR. Using promoter deletion and site directed mutagenesis analyses as well as gel shift assays, cooperative activation of the C/EBP and adjacent Sp1A, but not the Sp1B or AP1, sites by P is shown to confer P responsiveness leading to increased PrlR transcription.

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Section: Introductionmentioning

confidence: 99%

Progesterone induces expression of the prolactin receptor gene through cooperative action of Sp1 and C/EBP

Goldhar

Duan

Ginsburg

et al. 2011

Molecular and Cellular Endocrinology

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“…Crosstalk between PRLR and ERa occurs at several levels. For example, PRL and E 2 cooperatively enhance AP-1 activity (Gutzman et al 2005), and E 2 rapidly phosphorylates Stat5 (Fox et al 2009), while PRL activates the unliganded ER (Gonzalez et al 2009). …”

Section: Characteristics Of Prl and Prlrmentioning

confidence: 99%

Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy

LaPensee

Ben‐Jonathan

2010

Endocrine-Related Cancer

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Resistance to chemotherapy is a major complication in the treatment of advanced breast cancer. Estrogens and prolactin (PRL) are implicated in the pathogenesis of breast cancer but their roles in chemoresistance have been overlooked. A common feature to the two hormones is activation of their receptors by diverse compounds, which mimic or antagonize their actions. The PRL receptor is activated by lactogens (PRL, GH, or placental lactogen) originating from the pituitary, breast, adipose tissue, or the placenta. Estrogen receptors exist in multiple membrane-associated and cytoplasmic forms that can be activated by endogenous estrogens, man-made chemicals, and phytoestrogens. Here, we review evidence that low doses of PRL, estradiol (E 2 ), and bisphenol A (BPA) antagonize multiple anticancer drugs that induce cell death by different mechanisms. Focusing on cisplatin, a DNA-damaging drug which is effective in the treatment of many cancer types but not breast cancer, we compare the abilities of PRL, E 2 , and BPA to antagonize its cytotoxicity. Whereas PRL acts by activating the glutathione-S-transferase detoxification enzyme, E 2 and BPA act by inducing the antiapoptotic protein Bcl-2. The implications of these findings to patients undergoing chemotherapy are discussed.

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“…Two recent studies have addressed growth-promoting effects of PRL and E 2 and have examined signalling pathways involved (Gonzalez et al 2009, Chen et al 2010. PRL was shown to stimulate Ser118 phosphorylation of ER, the modification which was suggested to potentiate transcriptional activity of the unliganded ER or to stabilise ER allowing maintenance of a response to E 2 .…”

Section: Introductionmentioning

confidence: 99%

Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells

Rasmussen¹,

Frederiksen²,

Din³

et al. 2010

Endocrine-Related Cancer

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The pituitary hormone prolactin (PRL) plays an important role in mammary gland development. It was also suggested to contribute to breast cancer progression. In vivo data strongly supported a crucial role of PRL in promoting tumour growth; however, PRL demonstrated only a weak, if any, pro-proliferative effect on cancer cells in vitro. Several recent studies indicated that PRL action in vivo may be influenced by the hormonal milieu, e.g. other growth factors such as 17b-oestradiol (E 2 ). Here, we explored the potential interplay between PRL and E 2 in regulation of gene expression and cell growth. PRL alone induced either a weak or no proliferative response of T47D and BT-483 cells respectively, while it drastically enhanced cell proliferation in E 2 -stimulated cultures. Affymetrix microarray analysis revealed 12 genes to be regulated by E 2 , while 57 genes were regulated by PRL in T47D cells. Most of the PRL-regulated genes (42/57) were not previously described as PRL target genes, e.g. WT1 and IER3. One hundred and five genes were found to be regulated upon PRL/E 2 co-treatment: highest up-regulation was found for EGR3, RUNX2, EGR1, MAFF, GLIPR1, IER3, SOCS3, WT1 and AREG. PRL and E 2 synergised to regulate EGR3, while multiple genes were regulated additively. These data show a novel interplay between PRL and E 2 to modulate gene regulation in breast cancer cells.

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Activation of the unliganded estrogen receptor by prolactin in breast cancer cells

Cited by 56 publications

References 55 publications

Progesterone induces expression of the prolactin receptor gene through cooperative action of Sp1 and C/EBP

Progesterone induces expression of the prolactin receptor gene through cooperative action of Sp1 and C/EBP

Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy

Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells

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