EGFR dependent expression of STAT3 (but not STAT1) in breast cancer

Berclaz, Gilles; Altermatt, Hans Jörg; Rohrbach, Valeria; Siragusa, Antonino; Dreher, E.; Smith, Paul

doi:10.3892/ijo.19.6.1155

Cited by 77 publications

(85 citation statements)

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“…Activated STAT3 promotes breast cancer cell proliferation (Li and Shaw, 2002), and inhibits apoptosis . In human breast cancer tissue, elevated cytoplasmic and nuclear STAT3 (Berclaz et al, 2001) as well as nuclear tyrosine phosphorylated STAT3 (Diaz et al, 2006) has been reported. STAT5 has also been implicated in breast cancer but the levels of phosphorylated STAT5 were not significantly elevated in our model.…”

Section: Discussionmentioning

confidence: 99%

Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation

et al. 2006

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Overexpression and hyperactivation of the type I insulinlike growth factor receptor (IGF-IR) has been observed in human breast tumor biopsies. In addition, in vitro studies indicate that overexpression of IGF-IR is sufficient to transform cells such as mouse embryo fibroblasts and this receptor promotes proliferation and survival in breast cancer cell lines. To fully understand the function of the IGF-IR in tumor initiation and progression, transgenic mice containing human IGF-IR under a doxycyclineinducible MMTV promoter system were generated. Administration of 2 mg/ml doxycycline in the animals' water supply beginning at 21 days of age resulted in elevated levels of IGF-IR in mammary epithelial cells as detected by Western blotting and immunohistochemistry. Whole mount analysis of 55-day-old mouse mammary glands revealed that IGF-IR overexpression significantly impaired ductal elongation. Moreover, histological analyses revealed multiple hyperplasic lesions in the mammary glands of these 55-day-old mice. The formation of palpable mammary tumors was evident at approximately 2 months of age and was associated with increased levels of IGF-IR signaling molecules including phosphorylated Akt, Erk1/Erk2 and STAT3. Therefore, these transgenic mice provide evidence that IGF-IR overexpression is sufficient to induce mammary epithelial hyperplasia and tumor formation in vivo and provide a model to further understand the function of IGF-IR in mammary epithelial transformation.

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Section: Discussionmentioning

confidence: 99%

Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation

et al. 2006

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“…Many studies have suggested an association between STAT3 activation and breast tumorigenesis (20,35). Moreover, factors released from cancer cells may activate STAT3 in an autocrine manner and maintain tumor STAT3 activity and oncogenic potential (19,21,36,37).…”

Section: Rantes-mediated Stat3 Activationmentioning

confidence: 99%

“…18). High levels of constitutive STAT3 activation are thought to arise from autocrine stimulation (18)(19)(20)(21). Thus, interruption of constitutive STAT3 signaling in tumor cells will likely inhibit expression of several important classes of oncogenic proteins (22).…”

Section: Introductionmentioning

confidence: 99%

STAT3-RANTES Autocrine Signaling Is Essential for Tamoxifen Resistance in Human Breast Cancer Cells

Lee

et al. 2013

Molecular Cancer Research

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The acquisition of tamoxifen resistance is a major therapeutic problem in breast cancer. We developed a tamoxifen-resistant MCF-7 (TRM-7) cell line to elucidate the molecular mechanisms and factors associated with acquisition of such resistance. We showed that phosphorylation of STAT3 at tyrosine 705 (Y705) and RANTES expression are increased in response to tamoxifen in human breast cancer cells. On the basis of these results, we hypothesize that upregulated STAT3 phosphorylation and RANTES may be correlated with the development of drug resistance. Here, we showed that STAT3 and RANTES contribute to the maintenance of drug resistance. STAT3 phosphorylation is constitutively retained via a RANTES autocrine loop, which in turn upregulates antiapoptotic signals in TRM-7 cells. STAT3-RANTES autocrine signaling affected expression of anti-apoptotic BCL-2 family genes and prevented TRM-7 cells from undergoing programmed cell death by inhibiting PARP and caspase-9 cleavage. Subsequently, blockade of STAT3 and RANTES in TRM-7 cells resulted in reduction of antiapoptotic signals, which was rescued by exogenous RANTES treatment; drug resistance was also restored. Taken together, our results suggested that STAT3-RANTES autocrine signaling is essential for maintenance of drug resistance and inhibition of programmed cell death. These mechanisms of STAT3-RANTES autocrine signaling suggest a novel strategy for management of patients with tamoxifen-resistant tumors. Mol Cancer Res; 11(1); 31-42. Ó2012 AACR. IntroductionBreast cancer is the second most common cancer worldwide after lung cancer, the fifth most common cause of cancer death, and the leading cause of cancer death in women. The global burden of breast cancer exceeds that of all other cancers, and its incidence is increasing (1). In women younger than 50 years with breast cancer, chemotherapy increases the 15-year survival rate by 10%,

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“…PI-3 kinase and phospholipase C-dependent pathways were reported to mediate EGF-induced cell migration (Price et al, 1999). Activation of c-Src and Stat3 by EGF was shown to be associated with cellular transformation in certain cell types (Maa et al, 1995;Berclaz et al, 2001). Little is known about the pathway leading to apoptosis.…”

Section: Introductionmentioning

confidence: 99%

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

et al. 2003

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EGFR dependent expression of STAT3 (but not STAT1) in breast cancer

Cited by 77 publications

References 0 publications

Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation

Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation

STAT3-RANTES Autocrine Signaling Is Essential for Tamoxifen Resistance in Human Breast Cancer Cells

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

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