title: Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients.
abstract: Germline and somatic mutations play a crucial role in breast cancer (BC), driving the initiation, progression, response to therapy and outcome of the disease. Hormonal therapy is limited to patients with tumors expressing steroid hormone receptors, such as estrogen receptor (ER), nevertheless resistance often limits its success.The RET gene is known to be involved in neurocristopathies such as Hirschsprung disease and Multiple Endocrine Neoplasia type 2, in the presence of loss-of-function and gain-of-function mutations, respectively. More recently, RET over-expression has emerged as a new player in ER-positive (ER+) BC, and as a potential target to enhance sensitivity and avoid resistance to tamoxifen therapy.Therefore, targeting the RET pathway may lead to new therapies in ER+ BC. To this end, we have investigated the molecular mechanisms which underlie RET overexpression and its possible modulation in two BC cell lines, MCF7 and T47D, showing different RET expression levels. Moreover, we have carried out a pilot association study in 93 ER+ BC patients. Consistent with the adverse role of RET over-expression in BC, increased overall survival was observed in carriers of the variant allele of SNP rs2435357, a RET polymorphism already known to be associated with reduced RET expression.
authors.affiliation: UOC Medical Genetics, IRCCS Giannina Gaslini Institute, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Griseri
authors.affiliation: Unit of Medical Oncology, Department of Oncology, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Garrone
authors.affiliation: UOC Medical Genetics, IRCCS Giannina Gaslini Institute, Genoa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lo Sardo
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Department of Oncology, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Monteverde
authors.affiliation: UOC Medical Genetics, IRCCS Giannina Gaslini Institute, Genoa, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Rusmini
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Department of Oncology, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tonissi
authors.affiliation: Unit of Medical Oncology, Department of Oncology, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Merlano
authors.affiliation: Clinical Epidemiology, IRCCS AUO San Martino IST, Genoa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Department of Oncology, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lo Nigro
authors.affiliation: UOC Medical Genetics, IRCCS Giannina Gaslini Institute, Genoa, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D051096:Proto-Oncogene Proteins c-ret / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: RET gene; breast cancer; gene expression; resistance to hormonal therapy; single nucleotide polymorphism