Activated zinc transporter ZIP7 as an indicator of anti-hormone resistance in breast cancer.

ZIP7, a member of the ZIP family of zinc importers, resides on the endoplasmic reticulum membrane and transports zinc from intracellular stores to the cytoplasm after activation by CK2 phosphorylation on two serine residues (S275 and S276). ZIP7 is known to be required for the growth of anti-hormone resistant breast cancer models, especially those with acquired tamoxifen resistance developed from MCF-7. Using our new pSSZIP7 antibody which only recognises activated ZIP7 (pZIP7), we have demonstrated that the hyperactivation of ZIP7 is prevalent in tamoxifen-resistant breast cancer cells.

Dose-dependent change in biomarkers during neoadjuvant endocrine therapy with fulvestrant: results from NEWEST, a randomized Phase II study.

NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors) is the first study to compare biological and clinical activity of fulvestrant 500 versus 250 mg in the neoadjuvant breast cancer setting. We hypothesized that fulvestrant 500 mg may be superior to 250 mg in blocking estrogen receptor (ER) signaling and growth. A multicenter, randomized, open-label, Phase II study was performed to compare fulvestrant 500 mg (500 mg/month plus 500 mg on day 14 of month 1) versus fulvestrant 250 mg/month for 16 weeks prior to surgery in postmenopausal women with ER+ locally advanced breast cancer.

Elevated Src kinase activity attenuates Tamoxifen response in vitro and is associated with poor prognosis clinically.

Activated Src kinase may contribute to the progression and spread of breast cancers and recent in vitro evidence suggests a role for Src in acquired endocrine resistance. The purpose of this study was to investigate whether modulation of Src activity in endocrine-sensitive and endocrine-resistant breast cancer cells directly affected their phenotype and sensitivity to 4-hydroxy Tamoxifen (tamoxifen) and to determine whether Src activity in breast cancer tissue affected patient outcome. Expression of constitutively active Src in ER-positive, endocrine-sensitive MCF7 breast cancer cells resulted in the development of an aggressive phenotype, akin to that previously observed in cell models of Tamoxifen resistance, and, significantly, attenuated their response to tamoxifen.

Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival.

Drugs that target the insulin-like growth factor-I receptor (IGF-IR) and/or insulin receptor (IR) are currently under investigation for a variety of malignancies including breast cancer. Although we have previously reported that IGF-IR expression in primary breast tumors is common, the activation status of this receptor has not been examined in relation to survival. Phosphorylated IGF-IR/IR (P-IGF-IR/IR) and its downstream signaling partner phospho-S6 (P-S6) were evaluated immunohistochemically in tumor tissue microarrays representing 438 cases of invasive breast cancer.