Rosette Lidereau, PhD
Research Director, INSERM
2012-2013 BCRF Project:
(made possible by Delta Air Lines)
Institut National des Sciences et de la Recherche Médicale
Leader of the Department of Oncogenetics
Institut Curie/Hopital René Huguenin (IC/HRH)
Dr. Lidereau's BCRF-funded study focuses on breast cancers that spread (metastasize) to the lung and bone. It aims to identify, validate, and bring to the clinical setting new molecular markers for prognosis and diagnosis of organ-specific metastasis in breast cancer. These studies will determine the probability and extent of metastatic spread to different organs: metastasis to bone being a concern for long-term morbidity, and metastasis to visceral tissues a serious concern.
In 2012-2013, Dr. Lidereau's team will continue to pursue the study of KIND1 gene in breast cancer lung metastasis. Their analysis has uncovered additional functions of the gene that have not been reported to date, and the researchers will continue to characterize these newly identified functions. In addition to ongoing tests (including microarray analyses, migration/invasion assays, identification of the corresponding molecular pathways, etc.), Dr. Lidereau expects to perform a yeast-to-hybrid assay to identify the molecular partners of the wild-type kindlin-1 and the mutant form.
Towards their research on breast cancer bone metastasis, Dr. Lidereau's team has characterized several molecular markers associated with bone metastasis for which the prognostic value has been validated both at the RNA and protein level on large series of breast tumors (using microarrays, qRT-PCR and RPPA techniques). They will further examine the expression of these markers at the protein level by means of IHC techniques to develop tools that are better suits the translation to the clinics. To this end, a retrospective series of paraffin-embedded sections corresponding to 60 breast cancer patients with complete clinical follow-up has been collected.
Dr. Lidereau's team will also pursue the functional analysis of molecular markers associated with bone metastasis. Using a laboratory model of osteotropic breast tumors, they will investigate the effect of the inactivation of such markers on bone metastasis and osteolysis.
Mid-year Progress: In the last grant period, Dr. Lidereau's team published three manuscripts on breast cancer metastasis based on their BCRF-funded research. A new article on kindling-1 function in breast cancer is also under preparation.
In the continuation of the already performed work, during the first period of the current grant, Dr. Lidereau's team tested the putative role of two selected genes in bone metastasis using laboratory models and has focused their efforts on kindlin-1 role in lung metastasis of breast cancer.
The first attempts to validate two bone metastasis markers at the functional level were not conclusive. In contrast, the team's results on kindlin-1 function as a lung metastasis protein were significant. Kindlin-1 overexpression confers to cancer cells increased invasive capacities that are no longer observed in mutant kindlin-1 cells. In addition, by performing a yeast-two hybrid screen, this team identified new kindlin-1 molecular partners.
Dr. Rosette Lidereau received her PhD (1987) from Paris University, France. Since 1992 she has been a Research Director of the INSERM (Institut National des Sciences et de la Recherche Médicale) and since 2000, she has been in charge of the head of the INSERM Unit 735, located in the Institut Curie / Hopital René Huguenin (IC/HRH), Saint-Cloud, France. IC/HRH is a non-profit institution dedicated to cancer with a history of medical and biological expertise in breast cancer.
Dr. Lidereau has developed her scientific career on biology of breast cancer within the IC/HRH. Her former research interests are the evaluation of oncogenes' implication in breast tumorigenesis and their impact in clinics as prognostic and predictive factors in breast cancer. She is also the leader of the department of Oncogenetics in the IC/HRH and contributes to the clinics through diagnostics of cancer susceptibility genes mutations.