Journal
ONCOTARGET
Volume 7, Issue 18, Pages 26465-26479Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8417
Keywords
RET gene; breast cancer; single nucleotide polymorphism; gene expression; resistance to hormonal therapy
Categories
Funding
- Fondazione Umberto Veronesi
- Italian Association for Cancer Research [GI-13217]
- Italian Ministry of Health (Cinque per mille)
- Italian Ministry of Health (Ricerca Corrente)
Ask authors/readers for more resources
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 overexpression 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available