A functional screen for genes inducing epidermal growth factor autonomy of human mammary epithelial cells confirms the role of amphiregulin

Berquin, Isabelle M.; Dziubinski, Michele; Nolan, Garry P.; Ethier, Stephen P.

doi:10.1038/sj.onc.1204537

Cited by 34 publications

(33 citation statements)

References 47 publications

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“…Our studies and others have shown that immortal cells can acquire growth factor independence through acquisition of autocrine growth factors (Li et al, 1992;Shirakata et al, 2000;Berquin et al, 2001) or growth factor receptor overexpression (Woods Ignatoski et al, 1999;Worthylake et al, 1999;Nair et al, 2001). In the present study, we found that YB-1 lead to overexpression and activation of EGFR and to EGF-independent proliferation in HMECs.…”

Section: Discussionsupporting

confidence: 61%

“…To identify candidate genes that mediate growth factor autonomy, we expressed cDNAs from a breast cancer library into HMECs and selected cells that acquired EGF independence. Using this strategy, we have previously isolated a cDNA encoding the EGF family member amphiregulin, and we demonstrated that amphiregulin acts in an autocrine fashion through the EGFR in the donor breast cancer cell line (Berquin et al, 2001). The present report describes the isolation of another cDNA, encoding the transcriptional and translational regulator, YB-1.…”

Section: Discussionmentioning

confidence: 99%

“…However, libraryinfected H16N2 cells yielded three clones in one experiment. One of these clones contained the amphiregulin cDNA (Berquin et al, 2001). A second clone (H56b#2) contained two different cDNAs that were amplified by RT-PCR using vector-specific primers ( Figure 1a, lane 2).…”

Section: Isolation Of a Cdna Encoding Yb-1mentioning

confidence: 99%

“…The construction of a retroviral cDNA library from SUM-149PT breast cancer cells was described previously (Berquin et al, 2001). The SUM-149PT cell line was derived from a premenopausal patient with aggressive, inflammatory breast cancer.…”

Section: Isolation Of a Cdna Encoding Yb-1mentioning

confidence: 99%

“…To identify candidate genes expressed by breast cancer cells that mediate growth factor autonomy, we utilized an expression cloning strategy. A cDNA encoding the EGF family member amphiregulin was previously isolated using this strategy (Berquin et al, 2001). Here, we describe the isolation of another cDNA, encoding the transcriptional and translational regulator, Y-boxbinding protein 1 (YB-1).…”

Section: Introductionmentioning

confidence: 99%

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Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells

et al. 2005

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The epidermal growth factor receptor (EGFR) is linked to poor outcome in breast cancer, and resistance to hormonal therapy is often accompanied by activation of growth factor receptors. To investigate the mechanism(s) by which EGFR becomes activated in breast cancer, we screened a cDNA expression library for genes that mediate EGF-independent proliferation of human mammary epithelial cells (HMECs). We isolated the NSEP1 cDNA encoding Y-box-binding protein 1 (YB-1), a multifunctional transcriptional and translational regulator. This cDNA conferred growth factor independence to HMECs. YB-1-transduced cells overexpressed EGFR, but ErbB-2 (Her-2/neu) levels were unchanged. Moreover, EGFR was constitutively phosphorylated in the absence of exogenous ligand. In these cells, an EGFR-blocking antibody failed to inhibit proliferation, conditioned medium activity could not be detected, and the synthesis of EGFR ligands was reduced compared to parental cells. This suggests that EGFR is activated in a ligandindependent fashion. However, cell growth could be blocked with an ErbB kinase inhibitor, indicating that EGFR signaling plays a major role in YB-1-induced growth factor independence. Taken together, our results demonstrate that YB-1 overexpression can induce EGF independence in HMECs via activation of the EGFR pathway. This could represent one of the mechanisms by which YB-1 contributes to breast tumor aggressiveness.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Isolation Of a Cdna Encoding Yb-1mentioning

confidence: 99%

Section: Isolation Of a Cdna Encoding Yb-1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells

et al. 2005

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Mouse glioma gene expression profiling identifies novel human glioma‐associated genes

Gutmann

Huang²,

Hedrick³

et al. 2002

Annals of Neurology

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Based on previous studies demonstrating increased RAS activity in human astrocytomas, we developed a transgenic mouse model (B8) that targets an activated RAS molecule to astrocytes. Within 3 to 4 months after birth, these mice develop high-grade astrocytomas that are histologically identical to human astrocytomas. To characterize genetic events associated with B8 mouse astrocytoma formation, we employed comparative gene expression profiling of wild-type cultured mouse astrocytes, non-neoplastic B8 astrocytes, B8 astrocytoma cultures, and two other astrocytoma cultures from independently derived RAS transgenic mouse lines. We identified several classes of gene expression changes, including those associated with the non-neoplastic state in the B8 transgenic mouse, those associated with astrocytoma formation, and those specifically associated with only one of the three independently derived transgenic mouse astrocytomas. Differential expression of several unique genes was confirmed at the protein level in both the RAS transgenic mouse astrocytomas and two human glioblastoma multiforme cell lines. Furthermore, reexpression of one of these downregulated astrocytoma-associated proteins, GAP43, resulted in C6 glioma cell growth suppression. The use of this transgenic mouse model to identify novel genetic changes that might underlie the pathogenesis of human high-grade astrocytomas provides a unique opportunity to discover future targets for brain tumor therapy.

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Studies of dielectric characteristics and surface energies of spin‐coated polyimide films

2001

J of Applied Polymer Sci

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A two-step method, that is, polyamic acid formation with subsequent curing, was used to synthesize six kinds of polyimides. Dielectric constants and surface energies were investigated to determine the nature of the fluorinated and nonfluorinated polyimides. The dielectric constant decreased from 3.3 (at 100 kHz) for PMDA/ ODA to 2.6 (at 100 kHz) for 6FDA/4,4Ј-6F when the fluorine content increased from 0 to 30.7 wt %. Simultaneously, the water contact angle increased from 65°for PMDA/ ODA to 78°for 6FDA/4,4Ј-6F. Experimental results indicated that fluorinated polyimides contained a lower dielectric constant with improved water resistance. The surface energy values obtained from experiments agreed well with Holmes' correlation between surface energy and dielectric constant. The surface energies and dielectric constants were significantly affected by the polymer backbone structures, especially by the fluorination effect. Therefore, by choosing the appropriate monomers, polyimides of low dielectric constants with hydrophobic surfaces could be obtained.

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A functional screen for genes inducing epidermal growth factor autonomy of human mammary epithelial cells confirms the role of amphiregulin

Cited by 34 publications

References 47 publications

Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells

Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells

Mouse glioma gene expression profiling identifies novel human glioma‐associated genes

Studies of dielectric characteristics and surface energies of spin‐coated polyimide films

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