ArticlePloS one2010
Responsiveness to PI3K and MEK inhibitors in breast cancer. Use of a 3D culture system to study pathways related to hormone independence in mice.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 27 citations in OpenAlex.
- Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review).International journal of molecular medicine · 2025Review
- Modeling the developmental origins of pediatric cancer to improve patient outcomes.Disease models & mechanisms · 2021Review
- Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening.Journal of visualized experiments : JoVE · 2018Article
- AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins.Scientific reports · 2017Article
- hMENA(11a) contributes to HER3-mediated resistance to PI3K inhibitors in HER2-overexpressing breast cancer cells.Oncogene · 2016Article
- Activation of PI3K/Akt/mTOR signaling in the tumor stroma drives endocrine therapy-dependent breast tumor regression.Oncotarget · 2015Article
- Antiprogestins in gynecological diseases.Reproduction (Cambridge, England) · 2015Review
- Ligand-free estrogen receptor activity complements IGF1R to induce the proliferation of the MCF-7 breast cancer cells.BMC cancer · 2012Article
- The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer.Journal of translational medicine · 2012Article
- Inhibition of PI3K/mTOR leads to adaptive resistance in matrix-attached cancer cells.Cancer cell · 2012Article
- Unravelling the antimetastatic potential of pentoxifylline, a methylxanthine derivative in human MDA-MB-231 breast cancer cells.Molecular and cellular biochemistry · 2011Article
- Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression.Nature medicine · 2011Review
- LY294002 potentiates the anti-cancer effect of oxaliplatin for gastric cancer via death receptor pathway.World journal of gastroenterology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA significant proportion of breast cancer patients face failure of endocrine therapy due to the acquisition of endocrine resistance. We have explored mechanisms involved in such disease progression by using a mouse breast cancer model that is induced by medroxyprogesterone acetate (MPA). These tumors transit through different stages of hormone sensitivity. However, when cells from tumor variants were seeded on plastic, all were stimulated by progestins and inhibited by antiprogestins such as RU486. Furthermore, cells from a RU486-resistant tumor variant recovered antiprogestin sensitivity. HYPOTHESIS: A three-dimensional (3D) culture system, by maintaining differential cellular organization that is typical of each tumor variant, may allow for the maintenance of particular hormone responses and thus be appropriate for the study of the effects of specific inhibitors of signaling pathways associated with disease progression.
methodWe compared the behavior of tumors growing in vivo and cancer cells ex vivo (in 3D Matrigel). In this system, we evaluated the effects of kinase inhibitors and hormone antagonists on tumor growth. PRINCIPAL
findingsLY294002, a PI3K/AKT pathway inhibitor, decreased both tumor growth in vivo and cell survival in Matrigel in MPA-independent tumors with higher AKT activity. Induction of cell death by anti-hormones such as ICI182780 and ZK230211 was more effective in MPA-dependent tumors with lower AKT activity. Inhibition of MEK with PD98059 did not affect tumor growth in any tested variant. Finally, while Matrigel reproduced differential responsiveness of MPA-dependent and -independent breast cancer cells, it was not sufficient to preserve antiprogestin resistance of RU486-resistant tumors.
conclusionWe demonstrated that the PI3K/AKT pathway is relevant for MPA-independent tumor growth. Three-dimensional cultures were useful to test the effects of kinase inhibitors on breast cancer growth and highlight the need for in vivo models to validate experimental tools used for selective therapeutic targeting.
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