The laboratory studies the cellular mechanisms and genetic alterations involved in human cancer to better understand cancer, establish better classifications, identify stem cells and mutated genes, and identify diagnostic and prognostic markers that air max bw pas cher can be transferred into routine use. We study various types of human tumors.
In breast cancers, the teams of François Bertucci, Max Chaffanet/Anne Letessier, Emmanuelle Charafe Jauffret/Christophe Ginestier, and Marc Lopez work at identifying cancer stem cells, genomic alterations specific of molecular subtypes and histoclinical forms, prognostic and predictive markers, and to characterize the role and function of mutated genes. In vivo models such as transgenic and xenografted mice allow pre clinic studies.
The team of Palma Rocchi develops new therapeutic drugs against prostate cancer.
Identification of mutated genes in chronic and acute myeloid hematopoietic diseases is done by the team of Marie Joelle Mozziconacci, Anne Murati and Véronique Gelsi Boyer.
The team of Geraldine Guasch studies the molecular mechanism involved in tumor formation in epithelial transition zones, where one type of epithelium changes to another such as the cervix, anorectal air max enfant region, the esophagus stomach and the limbus of the eye. They have identified the presence of a stem cell niche in those regions and have established a mouse model that recapitulates tumor formation in those regions.
Finally, Emilie Mamessier and Claire Acquaviva’s team explores nike air max 90 circulating tumor cell (CTCs) heterogeneity to identify cells at high risk of seeding metastases.
Recent discoveries:A new oncogene in breast cancer : The ZNF703 oncogene at 8p12 is amplified in luminal B breast cancers.
Transition Zones Cancer and Stem Cells Circulating tumor cells cancer metastasesThe team’s effort is focused on understanding the various steps of breast carcinogenesis development. We study the hierarchical relationships between cells in normal and malignant breast epithelium in order to gain insight into the processes that underlie tumor initiation and development, and metastasis formation.
The primary aim is to characterize and to understand the regulation of mammary epithelial stem cells since these are likely to be the targets of cancer initiating events, and may be the underlying tumorigenic cells in breast cancers.
The secondary aim is to characterize the breast cancer stem cell population of various tumor subtypes to identify new markers and therapeutic targets and use the cancer stem cell concept at the clinical level to manage the disease.
Getting to the root of breast cancer The CSC model holds that tumors are organized in a cellular hierarchy in which « cancer stem cells » are the only cells with unlimited proliferation potential and with the capability of driving tumor growth and expansion. According to this model, cancers originate from the malignant transformation of an adult stem cell or progenitor through the dysregulation of the normally tightly regulated self renewal program. This leads to clonal stem/progenitor cell expansion generating cells that then undergo further genetic or epigenetic alterations to become fully transformed. As a consequence of this, tumors contain a cellular component of « cancer stem cells » (CSC) which retain key stem cell properties that initiate and drive carcinogenesis. Understanding the molecular basis for dysregulated self renewal is crucial for identification of targets for effective therapeutic intervention. Moreover, it will help us understand how the different molecular subtypes originate from CSC.
To study the different mechanisms that initiate oncogenesis, we perform in vitro and in vivo experiments in immunodeficient mice utilizing human mammary epithelial cells from patients that undergo reduction mammoplasties. These cells can be modified by lentiviral infection for the overexpression or downregulation of candidate genes.
The cancer stem cell : the breast cancer driver The cancer stem cell hypothesis modifies our conceptual approach of oncogenesis and described the CSC as « the cell to be killed » to eradicate breast cancer. To better characterize this cell population, we develop several strategies based on genomic, transcriptomic, and proteomic profiling. One current interest is to study the ALDEFLUOR positive population from different breast cancer subtypes to identify the different molecular mechanisms that sustain CSC biology. To validate functionally the different candidate genes/pathways identified, we develop a human breast tumor xenobank by transplantation of human primary tumor in immunodeficient mice. Moreover new therapeutic approaches targeting specifically the CSC population are evaluated utilizing these xenografts. J Clin Invest. Aldehyde Dehydrogenase 1 Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer. Clin Cancer Res. Retinoid signaling regulates breast cancer stem cell differentiation. Cell Cycle. Getting to the root of BRCA1 deficient breast air max pas cher cancer. nike air max bw Cell Stem Cell. stem cells : tools and models to rely on. BMC Cancer. 2009 Jun 25 ;9:202. Regulation of mammary stem/progenitor cells by PTEN/Akt/beta catenin signaling. PLoS Biol. cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. Cancer stem cells in breast : current opinion and future challenges. Pathobiology. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci U S A. [The cancer stem cell : the breast cancer driver]. Med Sci (Paris). 2007 Dec ;23(12):1133 9. Review. French.
Transition Zones Cancer and Stem Cells
Squamous cell carcinoma arise in stratified squamous epithelia of the body, and are one of the most common malignancies in humans with some of the poorest prognoses. They are frequently found at epithelial transition zones, where one type of epithelium changes to another such as the cervix, anorectal region, the esophagus stomach and the limbus of the eye.
The underlying mechanisms for this increased tumor susceptibility are unknown. Our current model focuses on anorectal transitional epithelium because we have created a tumor model in mice that recapitulates human anal transition zone tumors. Our research has identified an unsuspected link between the normal stem cells of the skin and an abnormally high incidence of tumors that arise in the transitional epithelium, in that chaussure nike air max both are regulated by the TGF signaling pathway. Our laboratory uses the transitional epithelium air max tn pas cher as a unique model to investigate the molecular basis for how normal epithelial stem cells become cancer stem cells. Our goal in working in a medical center is to establish a research program that uses basic discoveries of stem cell biology to impact several clinical programs here including oncology.
We use a variety of molecular, biochemical and tissue culture techniques, in vivo imaging and fluorescence activated cell sorting, as well as mouse transgenic and gene targeting (knockout) technology to address these various questions.