Transferrin receptor (CD71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen

Abstract

International audienceTransferrin 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 ( < 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

The prognostic significance of PELP1 expression in invasive breast cancer with emphasis on the ER-positive luminal-like subtype

“…Data on other biomarkers with strong relevance to breast cancer including oestrogen receptor (ERa), progesterone receptor (PgR), androgen receptor (AR), BRCA1, p53, FHIT, EGFR, HER2, HER3, HER4, E-cadherin, P-cadherin, basal and luminal cytokeratins (CKs) (CK5/6, CK14, CK18, CK19), neuroendocrine markers (Synaptophysin and Chromogranin A), cell cycle inhibitors (p21 and p27), p63, smooth muscle actin (SMA), MIB1, BCL2, FOXA1, Transferrin receptor (CD71), Thymidine kinase (TK1), and CARM1 protein expression were available [9,12,13].…”

RERG (Ras-like, oestrogen-regulated, growth-inhibitor) expression in breast cancer: a marker of ER-positive luminal-like subtype

“…Previously, we have reported on biomarkers selected for investigation on the basis of their biological function and their potential ability to distinguish different prognostic subclasses within the luminal group [5][6][7]. However, it is thought that novel approaches may be more appropriate for biomarker discovery in breast cancer.…”

Evaluation of CD71 Expression in Acute Leukemia in Egyptian Patients

“…CD71 overexpression has been reported in many neoplasms, including solid tumors such as lung [10,11] , bladder [12] , colon [13] , pancreas [14] and breast cancer [15,16] , gliomas [17] as well as hematological malignancies [18][19][20] .…”

“…Higher expression of CD71 has been identified as a negative prognostic marker for numerous solid tumor types [14,16] as well as for non-Hodgkin's lymphoma [21][22][23][24] . The high consumption of iron by the proliferating cells to act as co-factor for ribonucleotide reductase which is necessary for DNA synthesis makes the basis of targeting CD71 as an experimental anticancer therapy [25] .…”