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Rab proteins as breast cancer biomarkers
Portugal ( PorMSIC) - Nova University of Lisbon, Lisbon
CEDOC - CHRONIC DISEASES RESEARCH CENTER Campus SantAna Polo de Investigacao, NMS, UNL Rua Camara Pestana, no6 1150-082 Lisboa, Portugal
Teresa Margarida Barona
Type of Research Project
- Basic science
What is the background of the project?
Breast cancer is a heterogeneous disease with a varied morphological appearances, molecular features, behaviors and responses to therapy. It has different subtypes of Invasive ductal carcinona (IDC) namely: luminal A, luminal B, HER2+ and basal-like. Potential useful diagnostic tools at the clinical and molecular level are necessary for the early detection of breast cancer and for therapeutic follow up. We believe that Rab GTPase proteins have the potential to be useful at molecular level. Rab GTPases are master regulators of intracellular vesicle transport between different organelles of the endocytic and secretory pathways and are responsible for membrane maintenance and regulation in all cell types. These functions are central to understand carcinogenesis and to develop novel strategies to intervene in cancer cell behavior. Several Rabs have been implicated in the progression of breast cancer including Rab5A, Rab25, Rab27a and Rab27b, Rab31, Rab40b. Although there are several studies regarding the Rabs, the function and behavior of the remaining Rabs in human IDC is still unknown. A better understanding of molecular mechanisms of other Rab GTPases may open new opportunities for therapeutic intervention and better outcomes by the development of anticancer drugs for breast cancer.
What is the aim of the project?
We intend to explore the potential use of Rab proteins as a novel diagnostic tool at the molecular level in order to early detect breast carcinoma.
What techniques and methods are used?
We will use human samples patients who were diagnosed with IDC and recruited before any drug treatment. The same number of each tumor grade (GI, G2 and G3 according to Ellis-Elston classification) will be used and from each sample we have the data related to each molecular sub-type: luminal A, luminal B, basal-like and HER2+. Besides the formalin-fixed paraffin-embedded tissues for immunohistochemistry assays we will also collect frozen samples in order to have, from each pathological sample, both paraffin and freezing samples. We will preceed with the screening of Rab proteins in breast cancer tissues using specific antibodies against them by immunohistochemistry staining. We will also study the visual evaluation and statistical significance: Two independent observers, blind to clinical data, will classify the immunohistochemistry samples accordingly with the scale: 0 (negative), 1+ (faint, finely granular, cytoplasmatic immunostaining), 2+ (more intense, coarser, cytoplasmatic immunostaining) and 3+ (very intense immunostaining, filling the whole cytoplasm). The scale will be validated by ImageJ software and statistical analysis using the Spearman test and chi-square and program R.
What is the role of the student?
What are the tasks expected to be accomplished by the student?
All work will be done with supervision in the beginning, so that the student can understand the procedures and learn from observation. The student is expected to obtain the expression of the some Rab proteins in IDC paraffin-embedded samples using a scale defined by us. To validate it, using the ImageJ software and identify new Rabs which expression shows correlation with the tumors grade (grade I, II or III, accordingly with Ellis-Elston classification). We will have access to all histological data of patients, so we will also correlate the expression of these target Rabs in each molecular subtype with the estrogen and progesterone receptor status, HER2 status, vascular and neural invasion, lymph node and distant metastasis.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, the tutor will provide to the student the theoretical support.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Intracellular trafficking and bioinformatics knoledgment
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Students in biomedical fields
- Rakha; E. a; Reis-Filho; J. S.; Baehner; F.; Dabbs; D. J.; Decker; T.; Eusebi; V; Ellis; I. O. (2010). Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast cancer research?: BCR; 12(4); 207.
- Weigelt; B.; Geyer; F. C.; & Reis-Filho; J. S. (2010). Histological types of breast cancer: How special are they? Molecular Oncology.
- Recchi; C.; & Seabra; M. C. (2012). Novel functions for Rab GTPases in multiple aspects of tumour progression. Biochemical Society transactions; 40(6); 1398?403.
- Cheng; K. W.; Lahad; J. P.; Gray; J. W.; & Mills; G. B. (2005). Emerging role of RAB GTPases in cancer and human disease. Cancer Research.
- ALEX H. HUTAGALUNG AND PETER J. NOVICK (2011) Role of Rab GTPases in Membrane Traffic and Cell Physiology. Physiol Rev 91: 119?149.
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