Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer

Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Modern Pathology (Impact Factor: 6.36). 04/2007; 20(4):474-81. DOI: 10.1038/modpathol.3800760
Source: PubMed

ABSTRACT Tumours arising in BRCA1 mutation carriers and sporadic basal-like breast carcinomas have similar phenotypic, immunohistochemical and clinical characteristics. SOX2 is an embryonic transcription factor located at chromosome 3q, a region frequently gained in sporadic basal-like and BRCA1 germline mutated tumours. The aim of the study was to establish whether sox2 expression was related to basal-like sporadic breast tumours. Two hundred and twenty-six sporadic node-negative invasive breast carcinomas were immunohistochemically analysed for oestrogen receptor (ER), progesterone receptor (PR), CK5/6, EGFR, vimentin, HER2, ki67, p53 and sox2 using tissue microarrays. Tumours were considered to have basal-like phenotype if they were ER/HER2-negative and CK5/6 and/or EGFR-positive. Thirty cases of this series (13.7%) displayed a basal-like phenotype. Sox2 expression was observed in 16.7% of cases and was significantly more frequently expressed in basal-like breast carcinomas (43.3% in basal-like, 10.6% in luminal and 13.3% in HER2+ tumours, P<0.001). Moreover, Sox2 showed a statistically significant inverse association with ER and PR (P=0.001 and 0.017, respectively) and direct association with CK5/6, EGFR and vimentin (P=0.022, 0.005 and <0.001, respectively). Sox2 is preferentially expressed in tumours with basal-like phenotype and may play a role in defining their less differentiated/'stem cell' phenotypic characteristics.

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Available from: Yolanda Rodríguez-Gil, Aug 14, 2014
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    • "The transcription factor sex determining region Y-box 2 (SOX2) is well known to be one of the essential factors for inducing and maintaining the biological nature of stem cells (stemness), namely self-renewal and pluripotency as seen in adult neural progenitor cells (NPCs) [1]. On the other hand, SOX2 is expressed in a variety of cancers such as gastric cancer [2], small cell lung cancer [3], melanoma [4], esophangeal squamous cell carcinoma [5] and breast cancer [6], and may be involved in maintaining cancer stem cells (CSCs) which can self-renew, and have pluripotent and tumorigenic ability. However, biological roles of SOX2 in cancer cells remain undetermined. "
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    ABSTRACT: Sex-determining region Y-box 2 (SOX2) is well known as one of the "stemness" factors and is often expressed in cancers including breast cancer. In this study, we developed a reporter system using fluorescent protein driven by the promoter for SOX2 gene to detect and isolate living SOX2-positive cells. Using this system, we determined that SOX2 promoter activities were well correlated with SOX2 mRNA expression levels in 5 breast cancer cell lines, and that the cell population with positive SOX2 promoter activity (pSp-T(+)) isolated from one of the 5 cell lines, MCF-7 cells, showed a high SOX2 protein expression and high sphere-forming activity compared with very low promoter activity (pSp-T(low/-)). The pSp-T(+) population expressed higher mRNA levels of several stemness-related genes such as CD44, ABCB1, NANOG and TWIST1 than the pSp-T(low/-) population whereas the two populations expressed CD24 at similar levels. These results suggest that the cell population with SOX2 promoter activity contains cancer stem cell (CSC)-like cells which show expression profiles different from those of CSC-marker genes previously recognized in human breast cancers.
    Biochemical and Biophysical Research Communications 06/2013; 437(2). DOI:10.1016/j.bbrc.2013.06.038 · 2.28 Impact Factor
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    • "Breast cancer [56] Brain tumor [57] Bladder carcinoma, colon cancer, [53] hepatocellular carcinoma, lung adenocarcinoma, prostate cancer, seminoma Ovarian epithelial carcinoma [58] Sox1 Small cell lung cancer [60] Sox3 Small cell lung cancer [60] Klf4 Breast cancer [138] Acute lymphoblastic leukemia, [53] brain tumor, hairy cell leukemia, multiple myeloma, prostate cancer, yolk sac tumor Colorectal cancer [139] Klf5 Colon cancer [140] Nanog Germ cell tumors [62] Testicular carcinoma [63] CNS germinoma [64] Malignant cervical cancer [65] Lin28 Colon cancer, breast cancer, [66] lung cancer and cervical cancer Nr5a2 Breast adenoma [69] Gastric cancer [70] Endometrial cancer [71] Pancreatic ductal adenocacinoma [72] "
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    ABSTRACT: The discovery that overexpression of the transcription factors Oct4, Sox2, Klf4 and c-Myc reprograms differentiated cells into "induced pluripotent stem cells" (iPSCs) has extended our understanding of mechanisms required to maintain stem cell pluripotency and to drive differentiation. Subsequently, additional factors have been discovered that are able to induce a pluripotent state. Recently several groups have succeeded in reprogramming cancer cells to iPSC-like induced pluripotent cancer cells by use of the method established for the generation of iPSCs. This discovery highlighted several striking similarities between pluripotent stem cells and cancer cells, in turn implying that tumorigenesis and reprogramming are partly promoted by overlapping mechanisms. Thus, research on reprogramming might help unravel the mechanisms of carcinogenesis, and vice versa. This review gives an overview of the common features of pluripotent stem cells and cancer cells and summarizes the present state of knowledge in the field of cancer cell reprogramming.
    Biotechnology Journal 06/2012; 7(6):810-21. DOI:10.1002/biot.201100347 · 3.71 Impact Factor
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    • "However, the functional role of SOX2 in breast organogenesis remains still unexplored. SOX2 is over-expressed in breast cancer cells with increasing levels of expression in poorly differentiated cancer cells [62],[44]. Loss of function studies using SOX2-specific shRNA resulted in an inhibition of tumorigenic phenotype of MCF-7 breast cancer cells in xenograft studies in nude mice ([63]). These results give evidence that down-regulation of SOX2 in breast cancer cells can be used for clinical applications for the treatment of aggressive breast cancers. "
    Breast Cancer - Carcinogenesis, Cell Growth and Signalling Pathways, 11/2011; , ISBN: 978-953-307-714-7
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