Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients

Autor: Martino Monteverde, Marta Rusmini, Marco Merlano, Cristiana Lo Nigro, Alessandra Lo Sardo, Isabella Ceccherini, Paola Griseri, Ornella Garrone, Federica Tonissi, Paolo Bruzzi
Rok vydání: 2016
Předmět:
0301 basic medicine
congenital
hereditary
and neonatal diseases and abnormalities
medicine.medical_specialty
resistance to hormonal therapy
endocrine system diseases
Estrogen receptor
Breast Neoplasms
Pilot Projects
Multiple endocrine neoplasia type 2
Kaplan-Meier Estimate
Polymorphism
Single Nucleotide
Germline
Epigenesis
Genetic
03 medical and health sciences
breast cancer
0302 clinical medicine
Breast cancer
single nucleotide polymorphism
Cell Line
Tumor
Internal medicine
medicine
Humans
Epigenetics
neoplasms
Aged
Proportional Hazards Models
Aged
80 and over
business.industry
Proto-Oncogene Proteins c-ret
Middle Aged
medicine.disease
Gene Expression Regulation
Neoplastic
030104 developmental biology
Endocrinology
Oncology
RET gene
030220 oncology & carcinogenesis
gene expression
Cancer research
Hormonal therapy
Female
business
Tamoxifen
Research Paper
medicine.drug
Zdroj: Oncotarget
ISSN: 1949-2553
DOI: 10.18632/oncotarget.8417
Popis: 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.
Databáze: OpenAIRE
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