Transferrin receptor (CD71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen
Open accessAbstract
Transferrin receptor (CD71) is involved in the cellular uptake of iron and is expressed on cells with high proliferation. It may be implicated in promoting the growth of endocrine resistant phenotypes within ER+/luminal-like breast cancer. We used a panel of in vitro cell models of acquired resistance to tamoxifen (TAMR), Faslodex (FASR) or severe oestrogen deprivation (MCF-7X) and the ER+ luminal MCF-7 parental line to determine CD71 mRNA expression and to study transferrin (Tf) effects on in vitro tumour growth and its inhibition. Furthermore, CD71 protein expression was assessed in a well-characterized series of patients with invasive breast carcinoma using tissue microarrays. Our results demonstrated a striking elevation of CD71 in all cell models of acquired resistance. Exogenous Tf significantly promoted growth in MCF-7-X and MCF-7 cells but more so in MCF-7-X; this growth was significantly reduced by Faslodex (FAS) or a phosphoinositide-3 kinase inhibitor (LY294002). Increased CD71 expression was associated with poor NPI score, tumour proliferation, basal CKs, p53, EGFR, HER2, steroid receptor negativity and shortened breast cancer specific survival (P < 0.001). On multivariate analysis, CD71 was found to be an independent prognostic factor in the ER+ cohort of patients. In conclusion, therapies of current interest in breast cancer (e.g. FAS, PI3K-inhibitors) appear able to partially impact on transferrin/CD71-promoted growth, but further investigation of this important mitogenic mechanism may assist in designing new therapeutic strategies to target highly proliferative, endocrine resistant breast cancers. CD71 appears to be a candidate marker of a subgroup of ER+/luminal-like breast cancer characterised by poor outcome and resistance to tamoxifen.
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Upregulation of the Tf/TfR iron acquisition pathway is found in a variety of cancers, including breast and colon.
“Upregulation of this highly conserved iron acquisition pathway is found in a variety of cancers, including breast and colon [90,91,92,93].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [91]
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- Authors
- Habashy, H. O., Powe, D. G., Staka, C. M., Rakha, E. A., Ball, G., Green, A. R., Aleskandarany, M., Paish, E. C., Douglas Macmillan, R., Nicholson, R. I., Ellis, I. O., & Gee, J. M. W.
- Affiliations
- University of Nottingham (GB)
- Cardiff University (GB)
- Nottingham Trent University (GB)
- Corresponding author
- Ellis, Ian O.
- ORCID
- Venue
- Breast Cancer Research and Treatment
- Published
- 2009-02-24
- Volume
- 119
- Issue
- 2
- Pages
- 283-293
- ISSN
- 0167-6806 (ISSN-L)
- 1573-7217
- OpenAlex
- W2092206294
- Cited by
- 236
- References
- 44
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 10 · 2023: 20 · 2022: 15 · 2021: 24 · 2020: 19 · 2019: 26 · 2018: 11 · 2017: 20 · 2016: 17 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 13
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Breast Cancer Research and Treatment (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- transferrin receptor, breast cancer, tamoxifen resistance, endocrine therapy resistance, estrogen receptor-positive breast cancer, prognostic factors, transferrin, PI3K inhibitors, LY294002, fulvestrant, MCF-7 cells, tumour proliferation, breast cancer-specific survival, HER2, EGFR, p53
- MeSH terms
- Fulvestrant, Phosphoinositide-3 Kinase Inhibitors, Adult, Breast Neoplasms, Carcinoma, Chromones, Estradiol, Female, Flavonoids, Humans, Immunohistochemistry, Middle Aged, Morpholines, Neoplasm Invasiveness, Predictive Value of Tests, Receptors, Estrogen, Receptors, Transferrin, Retrospective Studies, RNA, Messenger, Tamoxifen, Time Factors, Transferrin, Biomarkers, Tumor, Antigens, CD, Gene Expression Regulation, Neoplastic, Proportional Hazards Models, Treatment Outcome, Risk Assessment, Antineoplastic Agents, Hormonal, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, Reverse Transcriptase Polymerase Chain Reaction, Mitogen-Activated Protein Kinases, Cell Line, Tumor, Tissue Array Analysis, Protein Kinase Inhibitors, Cell Proliferation, Kaplan-Meier Estimate
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