A study of the relationship of metabolic MR parameters to estrogen dependence in breast cancer xenografts

Liu, Ting; Nath, Kavindra; Liu, Weixia; Zhou, Rong; Chen, I‐Wei

doi:10.1002/nbm.3342

Cited by 4 publications

(5 citation statements)

References 49 publications

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“…These differences could be explained by lower mRNA expression of ChoK (α and β) and higher expression of PLA group 4A in basal tumor xenografts ( 61 ). In another experimental subcutaneous model expressing basaloid TNBC markers (HCC1806), phosphomonoesters (which include PCho) and lactate levels were modulated by tumor size ( 62 ).…”

Section: Ptdcho Metabolism In Tnbcmentioning

confidence: 99%

Key Players in Choline Metabolic Reprograming in Triple-Negative Breast Cancer

et al. 2016

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Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care. 1H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up and also to identify new targets for treatment. Several studies have shown an altered phosphatidylcholine (PtdCho) metabolism in TNBCs, both in patients and in experimental models. Upregulation of choline kinase-alpha, an enzyme of the Kennedy pathway that phosphorylates free choline (Cho) to phosphocholine (PCho), is a major contributor to the increased PCho content detected in TNBCs. Phospholipase-mediated PtdCho headgroup hydrolysis also contributes to the build-up of a PCho pool in TNBC cells. The oncogene-driven PtdCho cycle appears to be fine tuned in TNBC cells in at least three ways: by modulating the choline import, by regulating the activity or expression of specific metabolic enzymes, and by contributing to the rewiring of the entire metabolic network. Thus, only by thoroughly dissecting these mechanisms, it will be possible to effectively translate this basic knowledge into further development and implementation of Cho-based imaging techniques and novel classes of therapeutics.

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Section: Ptdcho Metabolism In Tnbcmentioning

confidence: 99%

Key Players in Choline Metabolic Reprograming in Triple-Negative Breast Cancer

et al. 2016

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“…4 , E2 along does not have much effect on cell proliferation after knockdown HER2, but this does not mean that the effect of tamoxifen is independent of ER in BT474 cells. Many previous studies have confirmed the reactivity of BT474 cells to estrogen [ 29 – 31 ]. In our study, the MTT assays were conducted in BT474 cells transfected with siRNA targeting HER2 24 h, and treated with 17β-E2 (10 nmol/L) and/or tamoxifen (TAM) (1 μmol/L) for another 48 h. BT474 is a cell that doubles for a long time.…”

Section: Discussionmentioning

confidence: 75%

C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells

Che

et al. 2018

BMC Cancer

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BackgroundTamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance.MethodsMTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence. SiRNA was used to examine the function of HER2 in of BT474 cells. An in vivo xenograft animal model was established to examine the role of c-Cbl in tumor growth.ResultsMTT and colony formation assay showed that BT474 cells are resistant to tamoxifen and T47D cells are sensitive to tamoxifen. Immunoprecipitation experiments revealed ER-c-Src-HER2 complex formation in BT474 cells but not in T47D cells. However, ER-c-Src-HER2 complex formation was detected after overexpressing HER2 in T47D cells and these cells were more resistant to tamoxifen. HER2 knockdown by siRNA in BT474 cells reduced ER-c-Src-HER2 complex formation and reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was also disrupted and tamoxifen resistance was reversed in BT474 cells by the c-Src inhibitor PP2 and HER2 antibody trastuzumab. Nystatin, a lipid raft inhibitor, reduced ER-c-Src-HER2 complex formation and partially reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was disrupted by overexpression of c-Cbl but not by the c-Cbl ubiquitin ligase mutant. In addition, c-Cbl could reverse tamoxifen resistance in BT474 cells, but the ubiquitin ligase mutant had no effect. The effect of c-Cbl was validated in BT474 tumor-bearing nude mice in vivo. Immunofluorescence also revealed ER-c-Src-HER2 complex formation was reduced in tumor tissues of nude mice with c-Cbl overexpression.ConclusionsOur results suggested that c-Cbl can reverse tamoxifen resistance in HER2-overexpressing breast cancer cells by inhibiting the formation of the ER-c-Src-HER2 complex.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4387-5) contains supplementary material, which is available to authorized users.

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“…Among the biochemical and molecular factors contributing to metabolic differences in BC subtypes, the expression of ER makes BC cells susceptible to estrogen-mediated effects on glucose and lactate metabolism [102]. In fact, the existence of a link between estrogen and lactate metabolism in BC cells has been well known for decades [103].…”

Section: Lactate In Bc Metabolism and Tumorigenesismentioning

confidence: 99%

The Significance of Microenvironmental and Circulating Lactate in Breast Cancer

Frisardi,

Canovi,

Vaccaro

et al. 2023

IJMS

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Lactate represents the main product of pyruvate reduction catalyzed by the lactic dehydrogenase family of enzymes. Cancer cells utilize great quantities of glucose, shifting toward a glycolytic metabolism. With the contribution of tumor stromal cells and under hypoxic conditions, this leads toward the acidification of the extracellular matrix. The ability to shift between different metabolic pathways is a characteristic of breast cancer cells and is associated with an aggressive phenotype. Furthermore, the preliminary scientific evidence concerning the levels of circulating lactate in breast cancer points toward a correlation between hyperlactacidemia and poor prognosis, even though no clear linkage has been demonstrated. Overall, lactate may represent a promising metabolic target that needs to be investigated in breast cancer.

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A study of the relationship of metabolic MR parameters to estrogen dependence in breast cancer xenografts

Cited by 4 publications

References 49 publications

Key Players in Choline Metabolic Reprograming in Triple-Negative Breast Cancer

Key Players in Choline Metabolic Reprograming in Triple-Negative Breast Cancer

C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells

The Significance of Microenvironmental and Circulating Lactate in Breast Cancer

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