Estrogenic activity of phenol red

Welshons, Wade V.; Wolf, Michael; Murphy, Catherine S.; Jordan, V. Craig

doi:10.1016/0303-7207(88)90072-x

Cited by 149 publications

(84 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Expression of pS2 in cells not treated with E2 but cultured in reg-DMEM (Fig. 1B) was probably due to the well-known estrogenic activity of phenol red, a pH indicator dye [10,11]. Close correlation between ERa and pS2 expressions suggested that, as expected, pS2 gene expression was a reliable indicator of ERa activity ( Fig.…”

Section: Methodssupporting

confidence: 62%

Unliganded estrogen receptor-α activates transcription of the mammary gland Na+/I− symporter gene

Alotaibi¹,

Yaman²,

Demirpençe³

et al. 2006

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The function of sodium iodide symporter (Na + /I À symporter, or NIS) in mammary epithelial cells is essential for the accumulation of I À in milk; the newborn's first source of I À for thyroid hormone synthesis. Furthermore, increased mammary gland NIS expression has previously been shown in human breast cancer. Several hormones and factors including all-trans-retinoic acid (tRA) regulate the expression of NIS. In this study, using breast cancer cell lines, we established that tRA-responsive NIS expression is confined to estrogen receptor-a (ERa) positive cells and we investigated the role of ERa in the regulation of NIS expression. We showed that the suppression of endogenous ERa by RNA interference downregulates NIS expression in ERa positive mammary cells. Besides, in an ERa negative cell line, reintroduction of ERa resulted in the expression of NIS in a ligand-independent manner. We also identified a novel estrogen-responsive element in the promoter region of NIS that specifically binds ERa and mediates ERa-dependent activation of transcription. Our results indicate that unliganded ERa (apo-ERa) contributes to the regulation of NIS gene expression. In mammary gland lactocytes, sodium/iodide (Na + /I À ) symport via NIS is required to secrete I À in mother's milk [1]. I À in milk is used by the newborn in thyroid hormone biosynthesis, and thus it plays an essential role in post-natal development of skeletal muscles, nervous system, and lungs [2]. In vivo experiments in mice have previously demonstrated that in normal physiology, NIS expression is strictly linked to mammary development in gestation, and to lactation [1]. Non-lactating mammary gland tissue in female mice does not express NIS unless animals receive subcutaneous oxytocin treatments for three consecutive days. On the other hand, a similar treatment in ovariectomized mice is not sufficient for NIS upregulation. In these surgically treated animals, administration of 17-b-estradiol (E2) together with oxytocin is essential for functional expression of NIS. The fact that E2 treatment was only essential in ovariectomized animals, whereas lactogenic hormones were sufficient for functional NIS expression in surgically untreated mice, suggested that ovary functions and endogenous estrogens are essential in upregulating NIS expression [1]. Unlike in non-lactating mammary gland tissue, in transgenic mice bearing experimental breast cancers triggered by Erb-B2/neu and ras oncogenes, functional expression of NIS significantly increases [1]. In the same study, human breast cancer specimens were also analyzed, and an increased NIS expression was detected in human invasive breast cancer and ductal carcinoma in situ, as compared to no expression of NIS in healthy breast samples obtained from reductive mammoplasty operations [1].Recent studies with an ERa+ mammary cell line model, MCF-7, have led to the identification of additional hormones or ligands that control transcriptional regulation of NIS. In this cell line, the symporter gene was shown to be indu...

show abstract

Section: Methodssupporting

confidence: 62%

Unliganded estrogen receptor-α activates transcription of the mammary gland Na+/I− symporter gene

Alotaibi¹,

Yaman²,

Demirpençe³

et al. 2006

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…To minimize the role of other activators of hTERT transcription, cells were cultured in medium without phenol red, which is known to present an E2-like activity (50) and supplemented with 5% fetal calf serum. We observed an increase in hTERT expression with large variations (Fig.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Activation of hTERT, the Human Telomerase Reverse Transcriptase, by Nuclear Factor of Activated T Cells

Chebel

Rouault

Urbanowicz

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Telomerase is essential for telomere maintenance, and its activation is thought to be a critical step in cellular immortalization and tumorigenesis. Human telomerase reverse transcriptase (hTERT) is a major component of telomerase activity. We show here that hTERT is expressed soon after lymphocyte activation and that its expression is inhibited by rapamycin, wortmannin, and FK506, which was the most potent inhibitor. These results suggest a potential role for the transcription factor nuclear factor of activated T cells (NFAT) in the regulation of hTERT expression. Five putative NFAT-binding sites were identified in the hTERT promoter. In luciferase assays, the hTERT promoter was activated by overexpressed NFAT1. Moreover, serial deletions revealed that the promoter activation was mainly due to a ؊40 NFAT1-binding site flanked by two SP1-binding sites. Mutation of the ؊40 NFAT-binding site caused a 53% reduction in the transcriptional activity of hTERT promoter. Simultaneous mutations of the ؊40 NFAT-responsive element together with one or both SP1-binding sites led to a more dramatic decrease in luciferase activity than single mutations, suggesting a functional synergy between NFAT1 and SP1 in hTERT transcriptional regulation. NFAT1 overexpression in MCF7 and Jurkat cell lines induced an increase in endogenous hTERT mRNA expression. Inversely, its down-regulation was induced by NFAT1 silencing. Furthermore, chromatin immunoprecipitation assay demonstrated that NFAT1 directly binds to two sites (؊40 and ؊775) in the endogenous hTERT promoter. Thus, we show for the first time the direct involvement of NFAT1 in the transcriptional regulation of hTERT.Telomeres are specialized structures located at the ends of linear mammalian chromosomes (1). The erosion of human telomeres at each cycle of cellular division is compensated for by de novo synthesis catalyzed by human telomerase reverse transcriptase (hTERT), 3 the catalytic subunit of a ribonucleoprotein complex called telomerase (2). Telomerase maintains telomeres by protecting them from exonucleases and ligases and by preventing illegitimate recombination (3). However, hTERT is also implicated in cell immortalization and tumorigenesis (4) through its telomere-lengthening activity, as well as by a mechanism independent of telomere length (5).Most normal human somatic tissues do not express hTERT, but germinal cells, several types of normally activated or proliferating cells, and tumor cells do (6 -13). In particular, lymphocytes exhibit telomerase activity in response to stimulation (14). Regulation of telomerase expression in these cells is likely to occur in the G 1 phase of the cell cycle as telomerase is inhibited by rapamycin, a compound that affects the mammalian target of rapamycin (mTOR) but is not inhibited by aphidicolin or hydroxyurea, substances that inhibit DNA synthesis (14 -16). Phosphorylation of hTERT and the resulting effects on its nuclear translocation and telomerase activity have been well described (17, 18). These post-translational modificati...

show abstract

“…These include epidermal growth factor (Pathak et al, 1982), hydrocortisone and insulin (Hug et al, 1984;Kern et al, 1984) and transferrin (Calvo et al, 1983 (Berthois et al, 1986;Welshons et al, 1988). These findings emphasise the importance of excluding phenol red from the culture conditions when undertaking in vitro studies to examine the activity of other potential weak oestrogens such as tamoxifen.…”

Section: Colony Formation By Er-negative Hs578t Cellsmentioning

confidence: 99%

Effects of 4-hydroxytamoxifen and a novel pure antioestrogen (ICI 182780) on the clonogenic growth of human breast cancer cells in vitro

Defriend¹,

Anderson²,

Bell³

et al. 1994

Br J Cancer

View full text Add to dashboard Cite

show abstract

Estrogenic activity of phenol red

Cited by 149 publications

References 17 publications

Unliganded estrogen receptor-α activates transcription of the mammary gland Na+/I− symporter gene

Unliganded estrogen receptor-α activates transcription of the mammary gland Na+/I− symporter gene

Transcriptional Activation of hTERT, the Human Telomerase Reverse Transcriptase, by Nuclear Factor of Activated T Cells

Effects of 4-hydroxytamoxifen and a novel pure antioestrogen (ICI 182780) on the clonogenic growth of human breast cancer cells in vitro

Contact Info

Product

Resources

About