Biological Effects of Adrenal Androgens on MCF-7 and BT-20 Human Breast Cancer Cells

Najid, A; Habrioux, G

doi:10.1159/000226830

Cited by 27 publications

(13 citation statements)

References 14 publications

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“…Nonetheless, some ER-positive BC cell lines, such as MCF-7 and MDA-MB-453, are growth stimulated by androgens and inhibited by anti-androgens (Birrell et al 1995, Cochrane et al 2014. Other data show a proliferative response of ER-positive BC cell lines to adrenal androgens (Poulin & Labrie 1986, Najid & Habrioux 1990, Boccuzzi et al 1992, Maggiolini et al 1999, Billich et al 2000.…”

Section: Figurementioning

confidence: 98%

Androgen receptor signaling pathways as a target for breast cancer treatment

Pietri¹,

Conteduca²,

Andreis³

et al. 2016

Endocrine-Related Cancer

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The androgen receptor (AR) is a ligand-dependent transcription factor, and its effects on breast range from physiological pubertal development and age-related modifications to cancer onset and proliferation. The prevalence of AR in early breast cancer is around 60%, and AR is more frequently expressed in ER-positive than in ER-negative tumors. We offer an overview of AR signaling pathways in different breast cancer subtypes, providing evidence that its oncogenic role is likely to be different in distinct biological and clinical scenarios. In particular, in ER-positive breast cancer, AR signaling often antagonizes the growth stimulatory effect of ER signaling; in triple-negative breast cancer (TNBC), AR seems to drive tumor progression (at least in luminal AR subtype of TNBC with a gene expression profile mimicking luminal subtypes despite being negative to ER and enriched in AR expression); in HER2-positive breast cancer, in the absence of ER expression, AR signaling has a proliferative role. These data represent the rationale for AR-targeting treatment as a potentially new target therapy in breast cancer subset using androgen agonists in some AR-positive/ER-positive tumors, AR antagonists in triple-negative/ AR-positive tumors and in combination with anti-HER2 agents or with other signaling pathways inhibitors (including PI3K/MYC/ERK) in HER2-positive/AR-positive tumors. Only the ongoing and future prospective clinical trials will allow us to establish which agents are the best option in every specific condition, keeping in mind that there is evidence of opposite androgens and AR agonist/antagonist drug effects on cell proliferation particularly in AR-positive/ER-positive tumors.

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Section: Figurementioning

confidence: 98%

Androgen receptor signaling pathways as a target for breast cancer treatment

Pietri¹,

Conteduca²,

Andreis³

et al. 2016

Endocrine-Related Cancer

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“…Epidemiological and experimental studies suggest that they might affect the growth of human breast tumours (Bulbrook et al, 1971;Wang et al, 1975;Segaloff et al, 1980;Zumoff et al, 1981;Helzlsouer et al, 1992). In vitro studies showed that they may exert a dual and opposite effect on the growth of breast cancer cells (Adams et al, 1981;Poulin & Labrie, 1986;Najid & Habrioux, 1990;Boccuzzi et al, 1992a). ADIOL is able to stimulate the in vitro growth of oestrogen-dependent breast cancer cell lines in steroid-free medium when added at the concentrations found in the plasma of post-menopausal women (Nahoul et al, 1985).…”

mentioning

confidence: 99%

5-En-androstene-3 β,17 β-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol

Boccuzzi

Brignardello²,

Monaco³

et al. 1994

Br J Cancer

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Summary Adrenal androgens show a dual and apparently opposite effect on the growth of oestrogenresponsive breast cancer: they stimulate growth on their own, but counteract the growth-stimulatory effect of oestrogens. Focusing on the inhibitory action we have studied the effects of 5-en-androstene-3p,17p-diol (ADIOL) on the growth of oestrogen-responsive MCF-7 breast cancer cells in the presence of oestrogens (oestradiol and diethylstilboestrol), antiestrogens (tamoxifen) and antiandrogens (hydroxyflutamide). The inhibition of oestrogen-stimulated growth, attained with nanomolar concentrations of ADIOL, was not modified by increasing concentrations of diethylstilboestrol up to 100 nm. This inhibition was counteracted by antiandrogens, which were unable to block the ADIOL stimulatory effect in steroid-free medium. On the other hand, in the presence of tamoxifen ADIOL showed an additive antiproliferative activity also in steroid-free medium, rather than the usual stimulatory effect. These results suggest that ADIOL stimulates breast cancer cell growth via oestrogen receptors, but inhibits oestrogen-stimulated growth via androgen receptors.Adrenal androgens, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS) and 5-en-androstene-3p,17p-diol (ADIOL), are the major secretory

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“…Neither G6PD activity nor cell growth is affected by DHEA in SR-cells; conversely, the growth of the SR+ cells is stimulated by DHEA, but G6PD activity is not affected. The stimulatory action of DHEA on cell growth depends on its metabolization to ADIOL, a compound which binds to ERs (Adams et al, 1981;Najid and Habrioux, 1990;Boccuzzi et al, 1992b, Pizzini et al, 1992. This result does not support the theory that DHEA plays a role in the growth of breast cancer through G6PD modulation.…”

Section: Discussionmentioning

confidence: 98%

“…Moreover, the use of a hormoneresponsive cell line obscures the mechanism of the action on cell growth because of the overlap of hormonal and non-hormonal effects. More precisely, the proliferative effects of DHEA that are due to ER binding of its metabolite ADIOL (Adams et al, 1981;Najid and Habrioux, 1990) may mask an antiproliferative action because of G6PD inhibition. In view of this, we evaluated DHEA DHEA and G6PD in breast cancer cells 591 action on G6PD activity and growth in both SR-negative and SRpositive cells.…”

Section: Discussionmentioning

confidence: 99%

“…DHEA effect on breast cancer growth may depend on its hormonal activity via steroid receptors (SR), as DHEA is metabolized in breast tissue to 5-en-androstene-3 P, 17 ,-diol (ADIOL), a compound with both oestrogenic and androgenic properties (Poortman et al, 1975;Hackenberg et al, 1993). However, the prevailing hormonal activity of DHEA is to stimulate cell growth via the oestrogen receptors (ERs) (Adams et al, 1981;Najid and Habrioux, 1990;Pizzini et al, 1992), whereas its antiproliferative effect, due to androgen receptor (AR) binding (Hackemberg et al, 1993), becomes appreciable only when ERs are blocked (Boccuzzi et al, 1993(Boccuzzi et al, , 1994. Besides the SR-mediated effects, DHEA has been shown to exert numerous activities in both physiological and pathological conditions via 'non-hormonal' mechanism(s) (Ebeling and Koivisto, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Role of glucose-6-phosphate dehydrogenase inhibition in the antiproliferative effects of dehydroepiandrosterone on human breast cancer cells

Monaco

Pizzini²,

Gatto³

et al. 1997

Br J Cancer

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Summary Epidemiological and experimental studies suggest that dehydroepiandrosterone (DHEA) exerts a protective effect against breast cancer. It has been proposed that the non-competitive inhibition of glucose-6-phosphate dehydrogenase (G6PD) contributes to DHEA antitumour action. We evaluated the effects of DHEA on G6PD activity and on the in vitro proliferation of two human breast cancer cell lines, MCF-7 (steroid receptor positive) and MDA-MB-231 (steroid receptor negative), in a serum-free assay. DHEA inhibition of G6PD was only found to occur at concentrations above 10 gm; at these high concentrations, the growth curve was parallel to the enzyme inhibition curve in both cell lines. In contrast, at concentrations in the in vivo breast tissue concentration range, neither cell growth nor enzyme activity was inhibited. The results failed to confirm DHEA's putative anti-tumour action on breast cancer through G6PD inhibition, as the enzyme blockade only becomes apparent at pharmacological concentrations of the steroid.

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Biological Effects of Adrenal Androgens on MCF-7 and BT-20 Human Breast Cancer Cells

Cited by 27 publications

References 14 publications

Androgen receptor signaling pathways as a target for breast cancer treatment

Androgen receptor signaling pathways as a target for breast cancer treatment

5-En-androstene-3 β,17 β-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol

Role of glucose-6-phosphate dehydrogenase inhibition in the antiproliferative effects of dehydroepiandrosterone on human breast cancer cells

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