Tamoxifen induces selective membrane association of protein kinase C epsilon in MCF-7 human breast cancer cells

Lavie, Yaakov; Zhang, Zu-chuan; Cao, Hui-ting; Han, Tian; Jones, Ralph C.; Liu, Yong‐Yu; Jarman, Michael; Hardcastle, Ian R.; Giuliano, Armando E.; Cabot, Myles C.

doi:10.1002/(sici)1097-0215(19980911)77:6<928::aid-ijc22>3.0.co;2-w

Cited by 48 publications

(27 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both genomic nuclear-initiated estrogen signaling (NIES) mediated by ER-α66 and non-genomic membrane-initiated estrogen signaling (MIES) mediated by non-ER-α66 or other signaling pathways participate in the anti-tumor effect of tamoxifen. The signaling proteins in the latter include protein kinase C (PKC)[27], TGF-β[28], calmodulin[29], c-myc[30], ceramide[31] and MAP kinases[32].…”

Section: Discussionmentioning

confidence: 99%

STAT3 mediates resistance of CD44+CD24-/low breast cancer stem cells to tamoxifen in vitro

Wang

Zhao

et al. 2012

J Biomed Res

View full text Add to dashboard Cite

We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro. The capacities for mammosphere formation and STAT3 expression of CD44+CD24−/low MCF-7 and MCF-7 were observed. The CD44+CD24−/low subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant (TAM-R) cells. Cell cycle, apoptosis, STAT3 and phospho-STAT3 changes were observed after treatment with tamoxifen. Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed. CD44+CD24−/low MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7. The CD44+CD24−/low subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7. Cell cycle changes, anti-apoptotic effects and STAT3 changes were also found. Meanwhile, the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen. It is concluded that STAT3 plays an essential role in breast cancer stem cells, which correlated with tamoxifen resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

STAT3 mediates resistance of CD44+CD24-/low breast cancer stem cells to tamoxifen in vitro

Wang

Zhao

et al. 2012

J Biomed Res

View full text Add to dashboard Cite

show abstract

“…Addition of ICI 164,384 to polarized rat uterine epithelial cell cultures altered vectoral protein secretion in a manner opposite to that observed for estradiol [36]. Also, antiestrogens, including the ICI compounds, can act through ER-independent mechanisms [37][38][39][40]. Collectively, observations can be interpreted to indicate that, in addition to disruption of ER function, the antiadenotrophic effects of ICI reported here could reflect changes in vectoral patterns of epithelial secretion and associated alterations in tissue microenvironment required to ensure morphogenetically critical stromal-epithelial interactions that support normal endometrial maturation [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Endometrial Development and Adenogenesis in the Neonatal Pig: Effects of Estradiol Valerate and the Antiestrogen ICI 182,7801

Tarleton

Wiley

Bartol

1999

Biology of Reproduction

View full text Add to dashboard Cite

In the pig, appearance of endometrial glands between birth (postnatal day [PND] 0) and PND 14 involves development of estrogen receptor-alpha-positive (ER+) phenotype by, and increased DNA synthesis in, nascent glandular epithelium (GE). To determine whether ER activation is required for this process, gilts were treated daily with either vehicle, the antiestrogen ICI 182,780 (ICI), estradiol-17beta valerate (EV), or both ICI and EV. Treatments began on PND 0, before onset of adenogenesis, or on PND 7, after onset of gland proliferation. Uteri obtained on PNDs 7 and 14 (study one) or on PND 14 (study two) were weighed; uterine histology was evaluated; DNA synthesis in luminal epithelium and GE was characterized by determining 5-bromo-2'-deoxyuridine (BrdU) labeling index; and patterns of ER mRNA expression were evaluated in situ (study one). Gland genesis was inhibited by ICI, which decreased gland penetration depth by PND 14 in study one, both endometrial thickness and BrdU-labeling index in GE in study two, and increased stromal cell compaction in both studies. Uterotropic effects of EV included increased gland development and epithelial BrdU labeling and decreased stromal compaction. These effects were inhibited by coadministration of ICI. Treatments did not alter ER mRNA expression, which remained limited to stroma and GE. Data indicate that endometrial maturation and adenogenesis in the neonatal pig require expression and activation of a functional ER system.

show abstract

“…Moreover, favorable responses in glioma are believed to be linked to the interaction of tamoxifen with protein kinase C (PKC) [58]. In MCF-7 human breast cancer cells, tamoxifen was shown to induce selective membrane association of PKC-epsilon [59], and in estrogen receptor-negative MDA-MB-231 cells, phosphatidic acid, a lipid second messenger, was generated in response to tamoxifen exposure [31,60]. In a human mammary fibroblast cell line, tamoxifen was shown to activate phospholipase C and D and elicit PKC translocation [61].…”

Section: Non-sphingolipid-associated Activities Of Tpe’smentioning

confidence: 99%

Tamoxifen regulation of sphingolipid metabolism—Therapeutic implications

Morad

Cabot

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

Self Cite

View full text Add to dashboard Cite

Tamoxifen, a triphenylethylene antiestrogen and one of the first-line endocrine therapies used to treat estrogen receptor-positive breast cancer, has a number of interesting, off-target effects, and among these is the inhibition of sphingolipid metabolism. More specifically, tamoxifen inhibits ceramide glycosylation, and enzymatic step that can adventitiously support the influential tumor-suppressor properties of ceramide, the aliphatic backbone of sphingolipids. Additionally, tamoxifen and metabolites N-desmethyltamoxifen and 4-hydroxytamoxifen, have been shown to inhibit ceramide hydrolysis by the enzyme acid ceramidase. This particular intervention slows ceramide destruction and thereby depresses formation of sphingosine 1-phosphate, a mitogenic sphingolipid with cancer growth-promoting properties. As ceramide-centric therapies are becoming appealing clinical interventions in the treatment of cancer, agents like tamoxifen that can retard the generation of mitogenic sphingolipids and buffer ceramide clearance via inhibition of glycosylation, take on new importance. In this review, we present an abridged, lay introduction to sphingolipid metabolism, briefly chronicle tamoxifen’s history in the clinic, examine studies that demonstrate the impact of triphenylethylenes on sphingolipid metabolism in cancer cells, and canvass works relevant to the use of tamoxifen as adjuvant to drive ceramide-centric therapies in cancer treatment. The objective is to inform the readership of what could be a novel, off-label indication of tamoxifen and structurally-related triphenylethylenes, an indication divorced from estrogen receptor status and one with application in drug resistance.

show abstract

Tamoxifen induces selective membrane association of protein kinase C epsilon in MCF-7 human breast cancer cells

Cited by 48 publications

References 21 publications

STAT3 mediates resistance of CD44+CD24-/low breast cancer stem cells to tamoxifen in vitro

STAT3 mediates resistance of CD44+CD24-/low breast cancer stem cells to tamoxifen in vitro

Endometrial Development and Adenogenesis in the Neonatal Pig: Effects of Estradiol Valerate and the Antiestrogen ICI 182,7801

Tamoxifen regulation of sphingolipid metabolism—Therapeutic implications

Contact Info

Product

Resources

About