Highly sensitive profiling of CD44+/CD24− breast cancer stem cells by combining global mRNA amplification and next generation sequencing: Evidence for a hyperactive PI3K pathway
Abstract
We performed next generation sequencing- and microarray-based gene expression profiling of CD44(+)/CD24(-)/CD45(-) breast CSCs (cancer stem cells) isolated from primary ERα-positive breast cancer. By combining semi-automated dissociation of human tumor tissue, magnetic cell sorting and cDNA amplification less than 500 CSCs were required for transcriptome analyses. Besides overexpressing genes involved in maintenance of stemness, the CSCs showed higher levels of genes that drive the PI3K pathway, including EGFR, HB-EGF, PDGFRA/B, PDGF, MET, PIK3CA, PIK3R1 and PIK3R2. This suggests that, in CSCs of ERα-positive breast cancer, the PI3K pathway which is involved in endocrine resistance is hyperactive.
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In estrogen receptor-alpha (ERα)-positive breast tumors, cancer stem cells express significantly lower levels of ERα, a phenotype associated with resistance to endocrine therapy, mechanistically linked to PI3K pathway hyperactivation.
“For example, in estrogen receptor-alpha (ERα)-positive breast tumors, CSCs have been shown to express significantly lower levels of ERα, a phenotype associated with resistance to endocrine therapy. This resistance has been mechanistically linked to Phosphoinositide 3-kinase (PI3K) pathway hyperactivation, which promotes proliferation and impairs responsiveness to hormonal agents [125].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [125]
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References 58 · Cited by 64
- Authors
- Hardt, O., Wild, S., Oerlecke, I., Hofmann, K., Luo, S., Wiencek, Y., Kantelhardt, E., Vess, C., Smith, G. P., Schroth, G. P., Bosio, A., & Dittmer, J.
- Affiliations
- Miltenyi Biotec (Germany) (DE)
- University Hospital in Halle (DE)
- Illumina (United States) (US)
- Illumina (United Kingdom) (GB)
- Corresponding author
- Dittmer, Jürgen
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 325
- Issue
- 2
- Pages
- 165-174
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2101008725
- Cited by
- 64
- References
- 58
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 2 · 2017: 4 · 2016: 7 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 1
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- breast cancer stem cells, CD44+/CD24- cells, PI3K signaling, ERα-positive breast cancer, endocrine therapy resistance, gene expression profiling, transcriptome, EGFR, MET, PIK3CA, PIK3R1, PIK3R2, HB-EGF, stemness genes, single-cell transcriptomics
- MeSH terms
- Breast Neoplasms, Estrogens, Female, Humans, Isoenzymes, Neoplasm Proteins, Neoplasms, Hormone-Dependent, RNA, Messenger, RNA, Neoplasm, Sensitivity and Specificity, Neoplastic Stem Cells, Gene Expression Regulation, Neoplastic, Immunophenotyping, Immunomagnetic Separation, Carcinoma, Ductal, Breast, Hyaluronan Receptors, Phosphatidylinositol 3-Kinases, Gene Expression Profiling, Nucleic Acid Amplification Techniques, Estrogen Receptor alpha, CD24 Antigen, Transcriptome
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