Breast cyst fluids increase the proliferation of breast cell lines in correlation with their hormone and growth factor concentration

Enriori, Pablo J.; Vázquez, Stella Maris; Chiauzzi, Violeta A.; Perez, Cecilia; Fischer, Carlos R.; Gori, Jorge R.; Etkin, Alberto E.; Calandra, Ricardo S.; Lüthy, Isabel Alicia

doi:10.1111/j.1365-2265.2005.02408.x

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…Similar to amphiregulin and TGF-α, EGF is reported to promote breast tumorigenesis through EGFR activation [31–33], and inhibition of EGF/EGFR signaling has been shown to exert anti-tumor effects for breast cancer [34, 35]. The EGF concentration of 100 ng/ml we used is within the range between 30 and 300 ng/ml that was observed in breast cyst fluids of adult women [36]. Furthermore, several other studies also used 100 ng/ml of EGF to investigate EGFR activation [31, 34, 35].…”

Section: Discussionmentioning

confidence: 99%

EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling

et al. 2019

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Breast cancers that express epidermal growth factor (EGF) receptors (EGFRs) are associated with poor prognosis. Our group recently showed in breast cancer patients that EGFR expression is strongly correlated with high tumor uptake of the glucose analogue, 18F-fluorodeoxyglucose (FDG). Here, we explored the cellular mechanism and signaling pathways that can explain the relation between EGFR and breast cancer cell glucose metabolism. FDG uptake, lactate production and hexokinase (HK) activity were measured, and proliferation assays and western blots were performed. EGF stimulated an increase of FDG uptake in EGFR-positive T47D and MDA-MB-468 cells, but not in MCF-7 cells. In T47D cells, the effect was dose-dependent and was accompanied by increased lactate production, indicating a shift toward glycolytic flux. This metabolic response occurred through enhanced HK activity and upregulated glucose transporter 1 (GLUT1) expression. EGFR stimulation also increased T47D cell proliferation. Blocking EGFR activation with BIBX1382 or gefitinib completely abolished both FDG uptake and proliferation effects. EGFR stimulation induced MAP kinase (MAPK) and PI3 kinase (PI3K) activation. Increased cell proliferation by EGFR stimulation was completely abolished by MAPK inhibition with PD98059 or by PI3K inhibition with LY294002. Increased FDG uptake was also completely abrogated by PI3K inhibition but was uninfluenced by MAPK inhibition. These findings suggest that the association between breast tumor EGFR expression and high FDG uptake might be contributed by stimulation of the PI3K pathway downstream of EGFR activation. This was in contrast to EGFR-mediated cell proliferation that required MAPK as well as PI3K signaling.

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Section: Discussionmentioning

confidence: 99%

EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling

et al. 2019

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“…Type I cysts have a BCF composition similar to intracellular fluids, with high levels of potassium ions and a low level of sodium ions (Na + /K + ratio <3), whereas Type II cysts, having an electrolyte composition similar to serum, show low‐potassium and high‐sodium ion concentrations (Na + /K + ratio >3), mainly related to changes in Na/K ATPase activity, a key enzyme in the development of GBCD . According to literature data suggesting apocrine changes in the epithelium lining the breast gross cysts as risk factors for the development of BC, the association of GBCD and BC risk is mainly referred to Type I apocrine cysts …”

Section: Introductionmentioning

confidence: 99%

Characterization of oversulfated chondroitin sulfate rich in 4,6‐O‐disulfated disaccharides in breast cyst fluids collected from human breast gross cysts

Mannello

Maccari

Ligi

et al. 2013

Cell Biochemistry & Function

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Glycosaminoglycans (GAGs) from breast cyst fluid (BCF) of gross cysts, subdivided into apocrine and flattened, directly collected from 27 gross-cystic-breast-disease (GCBD)-affected women were analysed. Heparan sulfate, not further investigated, and chondroitin sulfate were identified. This last polysaccharide, in a content of 25-27 µg ml(-1) BCF and having a high molecular mass (~20 000-22 000), was found rich in glucuronic acid (~96%-98%) and mainly sulfated in position 4 of the N-acetyl-galactosamine (~60%-64%). Moreover, the presence of ~19%-24% of uncommon 4,6-O-disulfated disaccharides CS-E inside the polysaccharide chains with a high charge density of ~1.15-1.20 was determined. No substantial differences between apocrine and flattened cysts were observed. The current study describes the first effort to examine the yield and distribution of complex macromolecules like GAGs in BCF, and the understanding of their structure may help explain some functions associated with physiological and pathological conditions.

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The combined influence of multiple sex and growth hormones on risk of postmenopausal breast cancer: a nested case-control study

et al. 2011

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IntroductionSex and growth hormones are positively associated with postmenopausal breast cancer risk. However, few studies have evaluated the influence of multiple hormones simultaneously.MethodsWe considered the roles of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate and prolactin and, secondarily, insulin-like growth factor 1 (IGF-1) and c-peptide in postmenopausal breast cancer risk among 265 cases and 541 controls in the prospective Nurses' Health Study. We created several hormone scores, including ranking women by the number of hormones above the age- and batch-adjusted geometric mean and weighting hormone values by their individual associations with breast cancer risk.ResultsWomen in the top versus bottom quintile of individual estrogen or androgen levels had approximately a doubling of postmenopausal breast cancer risk. Having seven or eight compared to zero hormones above the geometric mean level was associated with total (RR = 2.7, 95% CI = 1.3 to 5.7, P trend < 0.001) and estrogen receptor (ER)-positive (RR = 3.4, 95% CI = 1.3 to 9.4, P trend < 0.001) breast cancer risk. When comparing the top versus bottom quintiles of the score weighted by individual hormone associations, the RR for total breast cancer was 3.0 (95% CI = 1.8 to 5.0, P trend < 0.001) and the RR for ER-positive disease was 3.9 (95% CI = 2.0 to 7.5, P trend < 0.001). The risk further increased when IGF-1 and c-peptide were included in the scores. The results did not change with adjustment for body mass index.ConclusionsOverall, the results of our study suggest that multiple hormones with high circulating levels substantially increase the risk of breast cancer, particularly ER-positive disease. Additional research should consider the potential impact of developing risk prediction scores that incorporate multiple hormones.

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Breast cyst fluids increase the proliferation of breast cell lines in correlation with their hormone and growth factor concentration

Abstract: The stimulatory action of BCF on cell proliferation in a model of human breast epithelial cells could partly explain the increased incidence of breast cancer in cyst-bearing women.

Cited by 3 publications

References 42 publications

EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling

EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling

Characterization of oversulfated chondroitin sulfate rich in 4,6‐O‐disulfated disaccharides in breast cyst fluids collected from human breast gross cysts

The combined influence of multiple sex and growth hormones on risk of postmenopausal breast cancer: a nested case-control study

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