Foto del docente

Fulvia Farabegoli

Assistant professor

Department of Pharmacy and Biotechnology

Academic discipline: MED/04 Experimental Medicine and Pathophysiology


Keywords: EGCG green tea cancer breast carcinoma neuroblastoma chemoprevention

 Dr. Fulvia Farabegoli has been mainly involved in studies concerning the relationship betweenstructure and function of ribosomal genes in situ at ultrastructural level, performing and improvingmany histochemical and immunocytochemical methods. By means of these techniques Dr. FulviaFarabegoli investigated the role of ribosomal gene structural modifications in transcriptional control; the relationship between histone absence and the extended structure of ribosomal chromatin and the nucleolar components involved in ribosomal gene transcription (2,3,5,10,12,14,17,18). Other ultrastructural studies were conducted in collaboration with various research teams (7,8,13,15).

Dr. Fulvia Farabegoli also studied the relationship between ribosomal gene distribution, nucleic acid synthesis, nucleolar morphology and the cell cycle in order to demonstrate the utility of cytochemical AgNOR staining for acidic proteins associated with ribosomal genes in diagnosis and prognosis of human tumours (1,4,6,9,11,16).

Since June 1991 Dr. Fulvia Farabegoli has performed non radioactive in situ hybridization techniques in order to investigate chromosome aberrations in human neuroblastoma and paediatricALL. October 1992: Dr. Fulvia Farabegoli started a research project concerning breast cancer in order to investigate chromosome 1 aberrations in this neoplasm by dual targetFISH techniques. The results demonstrated that chromosome 1 aberrations with 1p36 underrepresentation was correlated with the DNA index value, histologic grade, high cerbB2 expression and low bcl2 expression (19,20). FISH analysis was also used to investigate the biopathologiccharacteristics of a group ofbreast carcinoma samples, previously screened for cerbB2 overexpression by immunohistochemistry. The results indicated that only amplified samples overexpressing cerbB2 were correlated to poor prognostic factors. In contrast, samples overexpressing cerbB2 without amplification had biologic characteristics similar to immunonegative samples (22). Dr. Fulvia Farabegoli has investigated the genetic evolution of breast carcinoma by two different approaches. The first project has been aimed at investigating several chromosome alterations (1, 8, 12,16, 17 and 18) in breast carcinoma progression in diploid and aneuploid samples by means of FISH techniques (23). The second study concerned Ductal Carcinoma In Situ (DCIS) alterations as detected by a LOHPCR techniques using microsatellite DNA sequences. This study has been conducted in collaboration with the Laboratoire d'Oncogénétique, Centre René Huguenin, SaintCloud, France, directed by Dr. Rosette Lidereau (24). Fourty seven breast carcinoma samples have also been investigated by Comparative Genomic Hybridization, in order to study the relation between genomic imbalance and biopathologic parameters currently used in breast cancer pathology. This study has been conducted in the Department of Pathology of the Free University Hospital, Amsterdam, The Netherlands (26). CGH investigated samples were also studied with respect to polymorphism of codon 72 of p53 protein and found to be related to poor prognosis (25).


Recent investigations concern SOCS2 protein in breast carcinoma. SOCS-2 expression was found to be correlated with low proliferation indicators in a group of 50 reast carcinoma samples (27). The relation between SOCS-2, proliferation and oestrogen receptor expression is currently under investigation in breast carcinoma cells in vitro (30).

A second research project concern the effects of EGCG, the most active principle present in green tea, on breast carcinma cells in vitro (28, 29) and the mechanisms by which EGCG is citotoxic to breast carcinoma cells resistant to tamoxifen (31, 32).  Synergism between EGCG and molecules obtained from edible plants (34) or synthetic drugs are currently investigated in collaboration with different research groups.

Green tea and EGCG, the most active principle present in green tea, are subject of extensive investigations, because of their activity as anti-inflammatory, antioxidant and chemopreventive agents. The chemopreventive avtivity of green tea has been demonstrated by epidemiologic studies and the cytotoxic, antiangiogenic and anti metastatic activity demonstrated in animals and in vitro studies. We found that EGCG was cytotoxic to breast carcinoma cells having the oestrogen receptors and EGCG was able to downregulate the oestrogen receptor signalling pathway. We also found that EGCG could circumvent drug-resistence in cells resistant to tamoxifen (the first line treatment in breast carcinoma patients showing oestrogen receptors) by modulating the proteins involved in drug-resistance.

EGCG can decrease multidrug resistance either by down-regulation or inactivation of proteins belonging to the MRP subfamily, physiologically involved in molecule transport. Furthermore EGCG can down-regulate EGFR signalling pathway, a very important signalling pathway highly activated in tamoxifen resistant cells.