Differential effects of the simian virus 40 early genes on mammary epithelial cell growth, morphology, and gene expression

Wolff, Jacques; Wong, Connie; Cheng, Helen; Poyet, Patrick; Butel, Janet S.; Rosen, Jeffrey M.

doi:10.1016/0014-4827(92)90405-w

Cited by 7 publications

(4 citation statements)

References 52 publications

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“…3). Previous studies indicate that repression of histone gene expression occurs with the activation of wt TP53 by UV radiation (80), whereas their expression is increased by the expression of the SV40 T antigen, which inactivates wt TP53 protein (81). It remains to be determined whether overexpression of cluster A genes in this subset of UM-SCC could result from altered TP53 function or activation or interactions with other TP53 family members or cofactors.…”

Section: Discussionmentioning

confidence: 95%

A Novel Nuclear Factor-κB Gene Signature Is Differentially Expressed in Head and Neck Squamous Cell Carcinomas in Association with TP53 Status

Lee

Yang

Yan

et al. 2007

Clinical Cancer Research

105

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Purpose: To determine if gene signatures differentially expressed in head and neck squamous cell carcinomas (HNSCC) are related to alterations in transcription factors nuclear factor-nB (NF-nB) andTP53previouslyassociatedwithdecreasedcelldeath,responsetotherapy,andworseprognosis. Experimental Design: Unique gene signatures expressed by HNSCC lines were identified by cDNA microarray, principal components, and cluster analyses and validated by quantitative reverse transcription-PCR (RT-PCR) and in situ hybridization. Bioinformatic analysis of the promoters and ontogeny of these clustered genes was done. Expression of proteins encoded by genes of a putative NF-nB signature, NF-nB p65, and TP53 were examined in HNSCC tissue specimens by immunostaining. Predicted promoter binding and modulation of expression of candidate NF-nB genes and cell survival were evaluated by p65 chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) knockdown. Results: Two groups of HNSCC exhibiting distinct gene signatures were identified: cluster A enriched for histone genes, with a higher prevalence of TP53 promoter binding motifs; and cluster B enriched for injury response genes with NF-nB regulatory motifs. Coexpression of cluster B proteins was observed with strong NF-nB phospho-p65 and weak TP53 staining, and NF-nB phospho-p65 was inversely associated with TP53 (P = 0.02). Promoter binding of the NF-nB signature genes was confirmed by p65 ChIP, and down-modulation of their expression and cell death were induced by p65 siRNA. Conclusion: NF-nB promotes expression of a novel NF-nB^related gene signature and cell survival in HNSCC that weakly express TP53, a subset previously associated with inactivated wild-typeTP53, greater resistance to chemoradiotherapy, and worse prognosis.

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Section: Discussionmentioning

confidence: 95%

A Novel Nuclear Factor-κB Gene Signature Is Differentially Expressed in Head and Neck Squamous Cell Carcinomas in Association with TP53 Status

Lee

Yang

Yan

et al. 2007

Clinical Cancer Research

105

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“…Our results are consistent with others, who have shown that transformation by oncogenes such as HPV E7 or LT which bind pRB was not able to induce TGF-P resistance (Valverius et al, 1989;Braun et al, 1990;Woodworth et al, 1990). Furthermore, it has been reported that TGF-P induced fibroblast growth inhibition may function independently of c-myc expression (Moses, 1992) and the mammary gland in general appears to be resistant to transformation induced by LT (Choi et al, 1987(Choi et al, , 1988Wolff et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Characterization of transforming growth factor‐β growth regulatory effects and receptors on bovine mammary cells

Woodward

Dumont

O’Connor-McCourt

et al. 1995

Journal Cellular Physiology

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Transforming growth factor-beta (TGF-beta) has been shown to inhibit mammary morphogenesis, growth, and differentiation in murine studies. We have characterized TGF-beta receptors and their autoregulation, and the growth response to TGF-beta 1 and TGF-beta 2 in cultured bovine mammary epithelium (MAC-T) and fibroblasts. Affinity labelling studies revealed that fibroblast and epithelial cells contained type I, II, and III (betaglycan) receptors, with the type III receptor being the predominant binding component. On both fibroblasts and epithelial cells, TGF-beta 1 and TGF-beta 2 had equal binding affinities for the type I and II receptors, but TGF-beta 2 had a higher affinity for the type III receptor. Also, preincubation of MAC-T cells with 50 pM TGF-beta 1 or TGF-beta 2 markedly downregulated TGF-beta receptors. Proliferative response was measured using both total DNA and 3H-thymidine incorporation. Both TGF-beta isoforms were effective in inhibiting proliferation of MAC-T cells and fibroblasts. Inhibition of proliferation was not altered following immortalization of fibroblasts with SV-40 Large-T-antigen (LT), even when the cells acquired a transformed phenotype. Inhibition of proliferation was not a result of cytotoxicity, as TGF-beta at concentrations 1,000-fold higher than ED50 levels did not increase cell death. Moreover, the inhibition was reversible as shown by return of cellular proliferation to control levels following TGF-beta removal. Although growth inhibition was not transient as culture of MAC-T cells in TGF-beta resulted in sustained inhibition of proliferation for at least 144 h.

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“…In the first experiment, we infected cells with a virus carrying the coding sequence of enhanced green fluorescent protein (GFP). Since viral infection has been reported to significantly influence morphology and molecular homeostasis of mammary epithelial cells [31,32,33,34], we expected alterations on cellular migration patterns as well.…”

Section: Experimental Datamentioning

confidence: 99%

Anomalous diffusion on dynamical networks: a model for interacting epithelial cell migration

Thurner

Wick

Hanel

et al. 2003

Physica A: Statistical Mechanics and its Applications

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Differential effects of the simian virus 40 early genes on mammary epithelial cell growth, morphology, and gene expression

Cited by 7 publications

References 52 publications

A Novel Nuclear Factor-κB Gene Signature Is Differentially Expressed in Head and Neck Squamous Cell Carcinomas in Association with TP53 Status

A Novel Nuclear Factor-κB Gene Signature Is Differentially Expressed in Head and Neck Squamous Cell Carcinomas in Association with TP53 Status

Characterization of transforming growth factor‐β growth regulatory effects and receptors on bovine mammary cells

Anomalous diffusion on dynamical networks: a model for interacting epithelial cell migration

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