Lithium‐stimulated proliferation and alteration of phosphoinositide metabolites in MCF‐7 human breast cancer cells

Welshons, Wade V.; Engler, Kathleen S.; Taylor, Julia A.; Grady, Leigh H.; Curran, Edward M.

doi:10.1002/jcp.1041650116

Cited by 33 publications

(17 citation statements)

References 56 publications

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“…It is difficult to compile a literature focusing on inverted-U dose-response curves, as these types of dose-response functions are common in endocrine studies and are often not identified in titles or abstracts as a noteworthy finding. Among those that have been reported, nonmonotonic dose-response curves can occur at several levels of organization, ranging from the biochemical based on in vitro studies (28,54,62,(70)(71)(72)(73)(74)(75) to the organ or system level based on in vivo studies (23,60,66,(76)(77)(78)(79)(80)(81)(82).…”

Section: Mechanisms Of Estrogen Action Predict Low-dose Effects Of Eedcsmentioning

confidence: 99%

“…Half-maximal stimulation of proliferative response occurred at approximately 1 pM E 2 in medium (0.272 ppt) in the low-dose range, whereas inhibition was induced at micromolar concentrations in the high-dose range. Estrogen-dependent cell proliferation and cytotoxicity were determined exactly as described in prior publications (72,138,139). Briefly, the very wide dose responses (54) were performed for E 2 by incubating the indicated cells in 24-well plates for 4 days in culture medium (phenol red-free medium, charcoal-stripped serum) plus E 2 at concentrations from 0.01 or 0.1 pM through 100 µM, with daily medium changes.…”

Section: Importance Of Valid Positive and Negative Controls For Endocmentioning

confidence: 99%

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Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity.

Welshons

Thayer

Judy

et al. 2003

Environ Health Perspect

806

488

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During the past decade a number of pesticides, industrial by-products, manufactured products such as plastics, and natural chemicals have been shown to disrupt the endocrine system. These chemicals are referred to as endocrine-disrupting chemicals (EDCs). These chemicals have received considerable attention, in part because endocrine disruption is a relatively unstudied area in toxicology and is only recently being taken into account in risk assessment. The focus here is on EDCs with estrogenic activity (EEDCs), which are chemicals that act as hormone mimics via estrogen receptor mechanisms; this is currently the largest group of known endocrine disruptors. The main purpose of this article is to present an overview of the mechanisms of hormone action that provide the basis for understanding how EEDCs have the potential to be biologically active at low, environmentally relevant doses. Our strategy is to discuss the receptor mechanisms mediating responses to a natural hormone, 17β-estradiol (E 2 ), and then to use this information as the basis for describing the low-dose effects of chemicals that disrupt the normal functioning of this hormonal system, either by mimicking, modulating, or antagonizing the activity of the hormone. We have chosen to use estrogen as our example because there is more known about the biology of estrogens and xenoestrogens than other components of the endocrine system for which there is evidence for disruption by environmental chemicals; however, the information presented here is applicable to endocrine disruptors that interfere with other hormonal systems.We will begin by briefly reviewing information concerning the relationship between dose, receptor occupancy, and responses (such as cell proliferation) after binding of E 2 to estrogen receptors (ER-α) in cultured human MCF-7 breast cancer cells. A number of specific factors influence the dose of an EEDC that reaches the target cells to produce a response. These factors include route of administration, absorption, distribution, metabolism, rate of clearance, plasma transport, cell uptake, affinity for estrogen receptor subtype in the cell, and the interaction of the ligand-receptor complex with tissue-specific factors comprising the transcriptional apparatus. This mechanistic information provides the basis for establishing the dose at the target site in cells (nuclear receptors associated with DNA or more recently identified receptors associated with the cell membrane) for an EEDC required to elicit a biological response similar to that produced by a dose of E 2 with equal estrogenic activity. Modeling that takes into account each of these factors would encompass physiologically based pharmacokinetic information (1), as well as quantitative structure-activity relationships (QSAR) (2,3). We have previously discussed the factors that influence access of E 2 and EEDCs from blood to estrogen receptors in cells elsewhere (4-6). Our primary focus in this review is on the latter part of the overall process that occurs once an estrogenic chemic...

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Section: Mechanisms Of Estrogen Action Predict Low-dose Effects Of Eedcsmentioning

confidence: 99%

Section: Importance Of Valid Positive and Negative Controls For Endocmentioning

confidence: 99%

Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity.

Welshons

Thayer

Judy

et al. 2003

Environ Health Perspect

806

488

View full text Add to dashboard Cite

show abstract

“…Although some of these data may be debatable, the idea is thus raised that lithium may have antitumor properties. These effects are however cell-type dependent: on the one hand, lithium stimulates cell proliferation in mammary tumour cells (11), and on the other, it inhibits cell proliferation in melanoma (12), hepatocellular carcinoma (13) and prostate cancer (7), and it blocks glioma cell migration and invasion in vitro (14). Lithium chloride can also induce apoptosis in several cell types (8,15), even if it has been reported to have anti-apoptotic, especially neuroprotective, effects in certain experimental settings (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Lithium induces mortality in medulloblastoma cell lines

et al. 2010

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Abstract. Lithium is the main therapeutic agent for the treatment of bipolar disorders but nerve cells are not the sole target of this drug. Indeed, lithium has been reported to target numerous cell types and to affect cell proliferation, differentiation and death. Lithium targets a variety of enzymes among which there is GSK-3ß and a number of cell responses elicited by lithium are mediated by the Wnt pathway that is involved in medulloblastoma (MB) pathogenesis. We studied the in vitro effects of lithium on two different MB cell lines: D283MED and DAOY. High doses of lithium inhibited GSK3-ß, decreased cell proliferation and induced nonapoptotic cell death in both cell lines independently by intracellular levels of ß-catenin that is consistently high only in D283MED. At clinical doses, the anti-neoplastic effects were observed only in this cell line, highlighting the importance of a specific molecular background in determining the target therapy response. In conclusion, lithium could be a promising drug in MB, but an accurate molecular profile predictive of drug response still needs to be clarified.

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“…Similar stimulation of growth by Rb, K and Na was not observed. Beside of hormone-dependent breast cancer cells MCF-7, lithium also stimulated the growth of further two hormone-dependent breast cancer cells ZR-75-1 and T47D, but not hormone-independent MDA-MB-231 cells or an estrogen-independent clone of MCF-7 cells [212]. Acute and chronic Ni 2+ exposure increased ER-positive breast cancer cell (MCF-7) growth [213].…”

Section: Metalsmentioning

confidence: 99%

Impact of Environmental Contaminants on Breast Cancer / Wpływ Zanieczyszczenia Środowiska Na Raka Piersi

Kráľová

Jampílek

2015

Ecological Chemistry and Engineering S

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Breast cancer is the most frequent cancer in women. It is believed that among the causes of breast cancer, hereditary factors account for only 5-10% of risk and the environmental exposures to environmental contaminants account for an additional 30-50% of risk. This paper summarizes findings related to the risk of breast cancer due to exposure to following environmental contaminants: polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dioxins, organochlorine pesticides, organophosphorous pesticides, bisphenol A, phthalates, parabens, organic solvents, atmospheric pollutants, alkylphenols, metals, ionizing radiation, electromagnetic field and light pollution. Results obtained in in vitro experiments with breast cancer cell lines and in vivo with model rodents as well as in population based case-control studies are presented and the mode of action of individual environmental contaminants on mammary gland is discussed. Attention is also devoted to the effects of the timing of exposure to environmental contaminants (mainly exposition during development of the mammary gland) on breast cancer risk. Outcomes of professional exposure to some environmental contaminants on breast cancer risk are analysed as well.

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Lithium‐stimulated proliferation and alteration of phosphoinositide metabolites in MCF‐7 human breast cancer cells

Cited by 33 publications

References 56 publications

Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity.

Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity.

Lithium induces mortality in medulloblastoma cell lines

Impact of Environmental Contaminants on Breast Cancer / Wpływ Zanieczyszczenia Środowiska Na Raka Piersi

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