HER-2 and NF-kappaB as the targets for therapy-resistant breast cancer.
HER-2 (also called ErbB2 or Neu) tyrosine kinase, one of the four members of ErbB receptor family (ErbB1, i.e., EGFR ErbB2, ErbB3 and ErbB4), plays a critical role in the control of diverse cellular functions involved in differentiation, proliferation, migration and cell survival via multiple signal transduction pathways. Overexpression of HER-2, observed in HER-2-positive breast cancer patients, is believed to cause the tumor resistance to an array of anti-cancer agents and poor prognosis. Although HER-2 antibodies have shown growth inhibitory effects, more efficient molecular targets against HER-2-mediated tumor resistance need to be developed. The molecular mechanisms underlying HER-2-mediated tumor resistance, especially the connections between HER-2 and therapy-resistant signaling networks, need to be further investigated. NF-kappaB, a key stress transcription factor that can initiate a pro-survival network, was found to be activated in many cancer cells overexpressing HER-2 and to be responsible for the radiation resistance in HER-2 transfected breast cancer cells. Recent findings in literature and data from this laboratory suggest a possible co-operation between HER-2 and NF-KB in signaling tumor resistance to radiotherapy. This review will discuss the mechanisms of HER-2 mediated NF-kappaB signaling pathway and potential target for therapeutic intervention.
Ahmed
Kazi M
KM
Division of Molecular Radiobiology, Purdue University School of Health Sciences, Purdue Cancer Center, West Lafayette, Indiana 47907, USA.
Cao
Ning
N
Li
Jian Jian
JJ
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism
D016328:NF-kappa B; D018719:Erb-b2 Receptor Tyrosine Kinases