Xenograft Model of Progressive Human Proliferative Breast Disease

Miller, Fred R.; Soule, Herbert D.; Tait, Larty; Pauley, Robert J.; Wolman, Sandra R.; Dawson, Peter J.; Heppner, Gloria H.

doi:10.1093/jnci/85.21.1725

Cited by 186 publications

(134 citation statements)

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“…The MCF10AT cell line has been derived from the spontaneously immortalized human normal breast epithelial cell line MCF10A cells by stable transfection with mutant T24-H-ras . These are pre-malignant but nontumorigenic cells (Basolo et al, 1991;Miller et al, 1993). In our preliminary experiments, we found that the endogenous APC protein level in MCF10A cells was much lower than in MCF10AT cells (data not shown).…”

Section: Silencing Of Apc Increases Lp-ber In the Pre-malignant Breasmentioning

confidence: 82%

Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cells

et al. 2006

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Our previous studies have shown that treatment with cigarette smoke condensate (CSC) transforms normal breast epithelial cell line, MCF-10A. In the present study, the mechanism of CSC-induced transformation of breast epithelial cells was examined. We first determined whether benzo[a]pyrene (B[a]P)-and CSC-induced levels of APC are capable of inhibiting long-patch base excision repair (LP-BER) since our earlier studies had shown that an interaction of APC with DNA polymerase b (pol-b) blocks strand-displacement synthesis. With the use of a novel in vivo LP-BER assay, it was demonstrated that increased and decreased APC levels in different breast cancer cell lines were associated with a decrease or increase in LP-BER activity, respectively. The effect of APC on LP-BER in malignant and pre-malignant breast epithelial cell lines was produced by either overexpression or knockdown of APC. Furthermore, it was shown that the decreased LP-BER in B[a]P-or CSC-treated premalignant breast epithelial cells is associated with an increased level of APC and decreased cell growth. Our results suggest that the decreased growth allows cells to repair the damaged DNA before mitosis, and failure to repair damaged DNA has the potential to transform premalignant breast epithelial cells.

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Section: Silencing Of Apc Increases Lp-ber In the Pre-malignant Breasmentioning

confidence: 82%

Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cells

et al. 2006

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“…7 Transformation of MCF-10A cells with an activated H-Ras oncogene resulted in premalignant MCF-10AT/MCF-10ANeoT cells (termed NeoT in the figures) 16 that never form tumors, but do form preneoplastic lesions in immunodeficient mice. 8,17 Subsequent serial xenografting in mice created MCF-10CA1a cells (termed CA1a in the figures). 8 These cells yielded a 100% incidence of tumors when transplanted into nude mice.…”

Section: Resultsmentioning

confidence: 99%

“…8,17 Subsequent serial xenografting in mice created MCF-10CA1a cells (termed CA1a in the figures). 8 These cells yielded a 100% incidence of tumors when transplanted into nude mice. 10 Stable transduction of MCF-10ANeoT cells with Y-box binding protein 1 YB-1 (MCF-10ANeoT-YB-1, termed YB-1 in figures) induced EMT.…”

Section: Resultsmentioning

confidence: 99%

Translational control of TWIST1 expression in MCF-10A cell lines recapitulating breast cancer progression

Vislovukh

Meng

et al. 2012

Oncogene

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TWIST1 is a highly conserved basic helix-loop-helix transcription factor that promotes epithelial --mesenchymal transition (EMT). Its misregulation has been observed in various types of tumors. Using the MCF-10A-series of cell lines that recapitulate the early stages of breast cancer formation and EMT, we found TWIST1 to be upregulated during EMT and downregulated early in carcinogenesis. The TWIST1 3 0 UTR contains putative regulatory elements, including miRNA target sites and two cytoplasmic polyadenylation elements (CPE). We found that miR-580, CPEB1, and CPEB2 act as negative regulators of TWIST1 expression in a sequence-specific and additive/cooperative manner.

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“…MCF-10A cells are derived from adherent cells from a mammary epithelial cell line produced from long-term culture in serum-free medium with low Ca 2þ concentration (44). In contrast with MCF-7 estrogen receptor-positive breast cancer cells (45), these cells are nontumorigenic in immunosuppressed mice (46). Mouse fibroblast cell lines NIH 3T3 (wt) and NIH 3T3 expressing constitutively active forms of BRAF V600E (kindly provided by Prof. R. Marais; ref.…”

Section: Cell Culturementioning

confidence: 99%

Isolation of a Novel Thioflavin S–Derived Compound That Inhibits BAG-1–Mediated Protein Interactions and Targets BRAF Inhibitor–Resistant Cell Lines

Enthammer

Papadakis

Gachet

et al. 2013

Molecular Cancer Therapeutics

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Protein-protein interactions mediated through the C-terminal Bcl-2-associated athanogene (BAG) domain of BAG-1 are critical for cell survival and proliferation. Thioflavin S (NSC71948)-a mixture of compounds resulting from the methylation and sulfonation of primulin base-has been shown to dosedependently inhibit the interaction between BAG-1 and Hsc70 in vitro. In human breast cancer cell lines, with high BAG-1 expression levels, Thioflavin S reduces the binding of BAG-1 to Hsc70, Hsp70, or CRAF and decreases proliferation and viability. Here, we report the development of a protocol for the purification and isolation of biologically active constituents of Thioflavin S and the characterization of the novel compound Thio-2. Thio-2 blocked the growth of several transformed cell lines, but had much weaker effects on untransformed cells. Thio-2 also inhibited the proliferation of melanoma cell lines that had become resistant to treatment with PLX4032, an inhibitor of mutant BRAF. In transformed cells, Thio-2 interfered with intracellular signaling at the level of RAF, but had no effect on the activation of AKT. Thio-2 decreased binding of BAG-1 to Hsc70 and to a lesser extent BRAF in vitro and in vivo, suggesting a possible mechanism of action. Given that tumors frequently develop resistance to kinase inhibitors during treatment, Thio-2 and related compounds may offer promising alternative strategies to currently available therapies.

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Xenograft Model of Progressive Human Proliferative Breast Disease

Abstract: The reproducible establishment of representative stages in early breast cancer progression from the MCF10 model offers a new opportunity to analyze critical events of carcinogenesis and progression in breast cancer.

Cited by 186 publications

References 0 publications

Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cells

Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cells

Translational control of TWIST1 expression in MCF-10A cell lines recapitulating breast cancer progression

Isolation of a Novel Thioflavin S–Derived Compound That Inhibits BAG-1–Mediated Protein Interactions and Targets BRAF Inhibitor–Resistant Cell Lines

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