Crosstalk events in the estrogen signaling pathway may affect tamoxifen efficacy in breast cancer molecular subtypes.
Steroid hormones are involved on cell growth, development and differentiation. Such effects are often mediated by steroid receptors. One paradigmatic example of this coupling is the estrogen signaling pathway. Its dysregulation is involved in most tumors of the mammary gland. It is thus an important pharmacological target in breast cancer. This pathway, however, crosstalks with several other molecular pathways, a fact that may have consequences for the effectiveness of hormone modulating drug therapies, such as tamoxifen. For this work, we performed a systematic analysis of the major routes involved in crosstalk phenomena with the estrogen pathway - based on gene expression experiments (819 samples) and pathway analysis (493 samples) - for biopsy-captured tissue and contrasted in two independent datasets with in vivo and in vitro pharmacological stimulation. Our results confirm the presence of a number of crosstalk events across the estrogen signaling pathway with others that are dysregulated in different molecular subtypes of breast cancer. These may be involved in proliferation, invasiveness and apoptosis-evasion in patients. The results presented may open the way to new designs of adjuvant and neoadjuvant therapies for breast cancer treatment.
Computational Genomics Department, National Institute of Genomic Medicine (INMEGEN), Mexico.
Guillermo
G
de Anda-Jáuregui
Computational Genomics Department, National Institute of Genomic Medicine (INMEGEN), Mexico.
Raúl A
RA
Mejía-Pedroza
Computational Genomics Department, National Institute of Genomic Medicine (INMEGEN), Mexico; Center for Complexity Sciences, National Autonomous University of México (UNAM), Mexico.
Jesús
J
Espinal-Enríquez
Computational Genomics Department, National Institute of Genomic Medicine (INMEGEN), Mexico; Center for Complexity Sciences, National Autonomous University of México (UNAM), Mexico. Electronic address: ehernandez@inmegen.gob.mx.
Enrique
E
Hernández-Lemus
D000465:Algorithms; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use*
D004967:Estrogens; D013629:Tamoxifen
Breast cancer; Estrogen signaling; Pathway crosstalk; Systems biology