Androgen-induced human breast cancer cell proliferation is mediated by discrete mechanisms in estrogen receptor-α-positive and -negative breast cancer cells

Lin, Hung Yun; Sun, Mingzeng; Lin, Cassie; Tang, Heng Yuan; London, David; Shih, Ai; Davis, Faith B.; Davis, Paul J.

doi:10.1016/j.jsbmb.2008.12.010

Cited by 76 publications

(62 citation statements)

References 43 publications

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“…Effects of tetrac formulations on MDA-MB-231 cell proliferation (cell count) in a perfusion bellows cell culture system. 16 Control cells proliferated throughout the 9 d study. Added at day 0 were unmodified tetrac (10 -6 M) and tetrac nanoparticulate (lot ZI-04-30NP) (tetrac equivalent in the nanoparticulate preparation was 10 -6 M).…”

Section: Resultsmentioning

confidence: 94%

“…MDA-MB-231 human breast cancer cells are nuclear ERα-and progesterone receptor-negative and have been examined by us in other experimental contexts. 16 We concentrated in the present studies on several panels of genes associated with cancer cell survival. Because thyroid hormone is anti-apoptotic 10,17,18 and tetrac is pro-apoptotic, 17 we searched in tetrac-treated tumor cells for expression of differentially-regulated, apoptosis-relevant genes.…”

Section: Discussionmentioning

confidence: 99%

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Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac)

Glinskii¹,

Glinsky²,

Lin³

et al. 2009

Cell Cycle

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109

126

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Section: Resultsmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac)

Glinskii¹,

Glinsky²,

Lin³

et al. 2009

Cell Cycle

Self Cite

109

126

View full text Add to dashboard Cite

“…Furthermore, non-responder tumors showed an up-regulation of network processes related to androgen receptor nuclear signaling: this suggests that tumor resistant cells could divert androgens to another cell proliferation signal to escape from aromatase cell cycle inhibition [29]. Sikora et al [30] hypothesized that androgens and their metabolites, independently of aromatase activity, may contribute to breast cancer growth.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling and prediction of response to hormonal neoadjuvant treatment with anastrozole in surgically resectable breast cancer

Mello-Grand

Singh

Ghimenti

et al. 2010

Breast Cancer Res Treat

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expression profiling and prediction of response to hormonal neoadjuvant treatment with anastrozole in surgically resectable breast cancer. Breast Cancer Research and Treatment, Springer Verlag, 2010, 121 (2), pp.399-411. <10.1007/s10549-010-0887-y>. CLINICAL TRIALGene expression profiling and prediction of response to hormonal neoadjuvant treatment with anastrozole in surgically resectable breast cancer Abstract Aromatase inhibition (AI) is the most effective endocrine treatment for breast cancer in post-menopausal patients, but a percentage of hormone receptor-positive cancers do not benefit from such therapy: for example, about 20% of patients treated with anastrozole do not respond and it is still impossible to accurately predict sensitivity. Our main goal was to identify a robust expression signature predictive of response to neoadjuvant treatment with anastrozole in patients with ER? breast cancer. At the same time, we addressed the question of delineating treatment effects and possible mechanisms of intrinsic resistance occurring in non-responder patients. We analyzed the transcriptome of 17 tru-cut biopsies before treatment and 13 matched surgical samples after 3 months treatment with anastrozole taken from ER? breast tumors. Molecular profiles were related to clinical response data. Treatment with anastrozole was associated with a decreased expression of genes relating to cell proliferation and an increased expression of genes relating to inflammatory processes. There was also an enrichment of induction of T-cell anergy, positive regulation of androgen signalling, synaptic transmission and vesicle trafficking in non-responders, and of cell cycle inhibition and induction of immune response in responders. We identified an expression signature of 77 probes (54 genes) that predicted response in 100% of our cases. Five of them were able to accurately predict response on an independent dataset (P = 0.0056) of 52 ER? breast cancers treated with letrozole. Ten fixed independent samples from the anastrozole study were also used for RT-qPCR validations. This study suggests that a relative small number of genes analysed in a pre-treatment biopsy may identify patients likely to respond to AI neoadjuvant treatment. This may have practical utility translatable to the clinics. Furthermore, it Maurizia Mello-Grand and Vijay Singh contributed equally to the work.Electronic supplementary material The online version of this article (doi:10.1007/s10549-010-0887-y) contains supplementary material, which is available to authorized users. delineates novel mechanisms of intrinsic resistance to AI therapy that could be further investigated in order to explore circumventing treatments.

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“…Interestingly, in the MCF-7 cell line, which is the most widely used AR þ / ER þ breast cancer cell model, different groups also reported androgens' antiproliferative (7,8,39,42,43) as well as proliferative effects (44,45). These lines of controversial evidence most likely are due to the complexity of the AR pathway and lack of acknowledgment of broad mechanisms of androgenic effects in breast cancer, in vivo and in intro.…”

Section: /Ermentioning

confidence: 99%

Activation of AR Sensitizes Breast Carcinomas to NVP-BEZ235's Therapeutic Effect Mediated by PTEN and KLLN Upregulation

Wang

et al. 2014

Molecular Cancer Therapeutics

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NVP-BEZ235 is a newly developed dual PI3K/mTOR inhibitor, being tested in multiple clinical trials, including breast cancer. NVP-BEZ235 selectively induces cell growth inhibition in a subset, but not all, breast cancer cell lines. However, it remains a challenge to distinguish between sensitive and resistant tumors, particularly in the pretreatment setting. Here, we used ten breast cancer cell lines to compare NVP-BEZ235 sensitivity and in the context of androgen receptor (AR) activation during NVP-BEZ235 treatment. We also used female SCID mice bearing breast tumor xenografts to investigate the beneficial effect of dihydrotestosterone/NVP-BEZ235 combination treatment compared with each alone. We found that AR-positive breast cancer cell lines are much more sensitive to NVP-BEZ235 compared with AR-negative cells, regardless of PTEN or PI3KCA status. Reintroducing AR expression in NVP-BEZ235 nonresponsive AR-negative cells restored the response. DHT/NVP-BEZ235 combination not only resulted in a more significant growth inhibition than either drug alone, but also achieved tumor regression and complete responses for AR þ /ER þ tumors. This beneficial effect was mediated by dihydrotestosterone (DHT)-induced PTEN and KLLN expression. Furthermore, DHT could also reverse NVP-BEZ235-induced side effects such as skin rash and weight loss. Our data suggest that AR expression may be an independent predictive biomarker for response to NVP-BEZ235. AR induction could add benefit during NVP-BEZ235 treatment in patients, especially with AR þ

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Androgen-induced human breast cancer cell proliferation is mediated by discrete mechanisms in estrogen receptor-α-positive and -negative breast cancer cells

Cited by 76 publications

References 43 publications

Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac)

Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac)

Gene expression profiling and prediction of response to hormonal neoadjuvant treatment with anastrozole in surgically resectable breast cancer

Activation of AR Sensitizes Breast Carcinomas to NVP-BEZ235's Therapeutic Effect Mediated by PTEN and KLLN Upregulation

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