BCL11A Expression in Breast Cancer

B-cell leukemia/lymphoma 11A (BCL11A) is a transcription factor that regulates the expression of genes involved in cell division or apoptosis. A link between high BCL11A expression and a worse prognosis has been demonstrated in patients with various cancers. The aim of this study was to investigate the expression pattern of BCL11A in breast cancer (BC) cases and mastopathy samples and to correlate the results with the clinicopathological data. The expression of the BCL11A protein was investigated using immunohistochemistry (IHC) on 200 cases of BC and 13 mastopathy samples. The level of BCL11A mRNA was determined using real-time PCR in 22 cases of BC and 6 mastopathy samples. The expression of BCL11A was also examined at the protein and mRNA levels in BC cell lines. A higher expression level of BCL11A in BC cases was shown compared to mastopathy samples. The expression level of BCL11A in BC cases and in the studied cell lines decreased with the increasing grade of histological malignancy (G). It was also negatively correlated with the primary tumor size. A significantly lower expression of BCL11A was found in BC that did not express estrogen or progesterone receptors and in triple-negative cases. The results of our research suggest that BCL11A may be relevant in the development of BC.

[1]  A. Angius,et al.  Deciphering clinical significance of BCL11A isoforms and protein expression roles in triple-negative breast cancer subtype , 2022, Journal of Cancer Research and Clinical Oncology.

[2]  A. Lánczky,et al.  Web-Based Survival Analysis Tool Tailored for Medical Research (KMplot): Development and Implementation , 2021, Journal of medical Internet research.

[3]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[4]  Lei Wei,et al.  Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer , 2020, Frontiers in Oncology.

[5]  Jia Yuan,et al.  miR‑574‑5p attenuates proliferation, migration and EMT in triple‑negative breast cancer cells by targeting BCL11A and SOX2 to inhibit the SKIL/TAZ/CTGF axis. , 2020, International journal of oncology.

[6]  Dan Zhou,et al.  BCL11A enhances stemness and promotes progression by activating Wnt/β-catenin signaling in breast cancer , 2019, Cancer management and research.

[7]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[8]  Bo Chen,et al.  circEPSTI1 as a Prognostic Marker and Mediator of Triple-Negative Breast Cancer Progression , 2018, Theranostics.

[9]  Kejing Zhang,et al.  MiR-137 Suppresses Triple-Negative Breast Cancer Stemness and Tumorigenesis by Perturbing BCL11A-DNMT1 Interaction , 2018, Cellular Physiology and Biochemistry.

[10]  Lina Jing,et al.  Combined diagnosis of breast cancer in the early stage by MRI and detection of gene expression , 2018, Experimental and therapeutic medicine.

[11]  Inkyung Jung,et al.  Probing the interaction between the histone methyltransferase/deacetylase subunit RBBP4/7 and the transcription factor BCL11A in epigenetic complexes , 2017, The Journal of Biological Chemistry.

[12]  J. Guan,et al.  Breast Cancer: Multiple Subtypes within a Tumor? , 2017, Trends in cancer.

[13]  D. Hendrix,et al.  Transcription Factor CTIP1/ BCL11A Regulates Epidermal Differentiation and Lipid Metabolism During Skin Development , 2017, Scientific Reports.

[14]  D. Hendrix,et al.  Transcription Factor CTIP1/ BCL11A Regulates Epidermal Differentiation and Lipid Metabolism During Skin Development , 2017, Scientific Reports.

[15]  Li-jun Ling,et al.  Shikonin reduces tamoxifen resistance through long non-coding RNA uc.57 , 2017, Oncotarget.

[16]  Li-juan Wang,et al.  Inhibition of FOXQ1 induces apoptosis and suppresses proliferation in prostate cancer cells by controlling BCL11A/MDM2 expression. , 2016, Oncology reports.

[17]  P. Dzięgiel,et al.  Expression of matrix metalloproteinase 2 (MMP-2), E-cadherin and Ki-67 in metastatic and non-metastatic canine mammary carcinomas , 2016, Irish Veterinary Journal.

[18]  Yi-long Wu,et al.  The BCL11A-XL expression predicts relapse in squamous cell carcinoma and large cell carcinoma. , 2015, Journal of thoracic disease.

[19]  S. Orkin,et al.  Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. , 2015, Current opinion in genetics & development.

[20]  R. Gelber,et al.  Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015 , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  S. Chin,et al.  BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells , 2015, Nature Communications.

[22]  K. Baggerly,et al.  Reverse-phase protein array for prediction of patients at low risk of developing bone metastasis from breast cancer. , 2014, The oncologist.

[23]  Haley O. Tucker,et al.  Dendritic cell fate is determined by BCL11A , 2014, Proceedings of the National Academy of Sciences.

[24]  C. Perou,et al.  Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[25]  Yi-long Wu,et al.  BCL11A overexpression predicts survival and relapse in non-small cell lung cancer and is modulated by microRNA-30a and gene amplification , 2013, Molecular Cancer.

[26]  Ansuman T. Satpathy,et al.  Bcl11a Controls Flt3 Expression in Early Hematopoietic Progenitors and Is Required for pDC Development In Vivo , 2013, PloS one.

[27]  A. Giuliani,et al.  MicroRNA-486-3p Regulates γ-Globin Expression in Human Erythroid Cells by Directly Modulating BCL11A , 2013, PloS one.

[28]  Shannon Burke,et al.  Bcl11a is essential for lymphoid development and negatively regulates p53 , 2012, The Journal of experimental medicine.

[29]  Shelley M Enger,et al.  Impact of Breast Cancer Subtypes and Treatment on Survival: An Analysis Spanning Two Decades , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[30]  Wei Gu,et al.  Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence , 2012, Cell.

[31]  M. Majchrzak,et al.  Ceramide galactosyltransferase (UGT8) is a molecular marker of breast cancer malignancy and lung metastases , 2010, British Journal of Cancer.

[32]  Kaoru Tanaka,et al.  FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth. , 2010, Cancer research.

[33]  L. Medeiros,et al.  Chronic lymphocytic leukemia With t(2;14)(p16;q32) involves the BCL11A and IgH genes and is associated with atypical morphologic features and unmutated IgVH genes. , 2009, American journal of clinical pathology.

[34]  Y. Hsueh,et al.  Expression of zinc finger transcription factor Bcl11A/Evi9/CTIP1 in rat brain , 2007, Journal of neuroscience research.

[35]  R. Siebert,et al.  Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11AXL protein are frequent in primary mediastinal B-cell lymphoma , 2006, Leukemia.

[36]  L. Staudt,et al.  Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells , 2006, Molecular Cancer.

[37]  Takuro Nakamura,et al.  Bcl11a is essential for normal lymphoid development , 2003, Nature Immunology.

[38]  D G Oscier,et al.  The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. , 2001, Blood.

[39]  T. Nakamura,et al.  Human EVI9, a homologue of the mouse myeloid leukemia gene, is expressed in the hematopoietic progenitors and down-regulated during myeloid differentiation of HL60 cells. , 2000, Genomics.

[40]  D. Largaespada,et al.  Evi9 Encodes a Novel Zinc Finger Protein That Physically Interacts with BCL6, a Known Human B-Cell Proto-Oncogene Product , 2000, Molecular and Cellular Biology.

[41]  W. Remmele,et al.  [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. , 1987, Der Pathologe.

[42]  Victor Trevino,et al.  A New Gene Expression Signature for Triple-Negative Breast Cancer using Frozen Fresh Tissue before Neoadjuvant chemotherapy , 2017, Molecular medicine.

[43]  Yangqiu Li,et al.  Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines. , 2013, Biomedical reports.

[44]  Yan-fang Gao,et al.  Downregulation of BCL 11 A by siRNA induces apoptosis in B lymphoma cell lines , 2012 .

[45]  Sunil R. Lakhani,et al.  WHO classification of tumours of the breast , 2012 .

[46]  R. Gascoyne,et al.  The BCL11AXL transcription factor: its distribution in normal and malignant tissues and use as a marker for plasmacytoid dendritic cells , 2006, Leukemia.

[47]  D. Steinemann,et al.  The BCL 11 gene family : involvement of BCL 11 A in lymphoid malignancies , 2001 .

[48]  E. Somers International Agency for Research on Cancer. , 1985, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[49]  L. Frati,et al.  Oncotargets and Therapy Dovepress Triple-negative Breast Cancer: New Perspectives for Targeted Therapies , 2022 .