Phenotypic and Molecular Characterization of MCF10DCIS and SUM Breast Cancer Cell Lines

Barnabas, Nandita; Cohen, Dalia

doi:10.1155/2013/872743

Cited by 59 publications

(59 citation statements)

References 99 publications

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“…The SUM159PT cell line was originally developed from a primary tumor in a patient with estrogen receptor-negative, progesterone receptor-negative, and HER2-negative anaplastic carcinoma of the breast [41]. SUM159PT cells are highly invasive and tumorigenic [42]. The MCF10DCIS.com cell line was derived from a tumor originating from xenografting premalignant MCF10AT cells into severe combined immunodeficient mice [43].…”

Section: Resultsmentioning

confidence: 99%

Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells

Wise

Duhachek-Muggy

et al. 2016

Breast Cancer Res Treat

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Purpose Metastatic breast cancer cells are exposed to stress of detachment from the extracellular matrix (ECM). Cultured breast cancer cells that survive this stress and are capable of anchorage-independent proliferation form mammospheres. The purpose of this study was to explore a link between mammosphere growth, ECM gene expression, and the protein quality control system in the endoplasmic reticulum (ER). Methods We compared the mRNA and protein levels of ER folding factors in SUM159PT and MCF10DCIS.com breast cancer cells grown as mammospheres versus adherent conditions. Publicly available gene expression data for mammospheres formed by primary breast cancer cells and for circulating tumor cells (CTCs) were analyzed to assess the status of ECM/ER folding factor genes in clinically relevant samples. Knock-down of selected protein disulfide isomerase (PDI) family members was performed to examine their roles in SUM159PT mammosphere growth. Results Cells grown as mammospheres had elevated expression of ECM genes and ER folding quality control genes. CTC gene expression data for an index patient indicated that upregulation of ECM and ER folding factor genes occurred at the time of acquired therapy resistance and disease progression. Knock-down of PDI, ERp44, or ERp57, three members of the PDI family with elevated protein levels in mammospheres, in SUM159PT cells partially inhibited the mammosphere growth. Conclusion Breast cancer cell survival and growth under detachment conditions require enhanced assistance of the ER protein folding machinery. Targeting ER folding factors, in particular members of the PDI family, may improve the therapeutic outcomes in metastatic breast cancer.

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Section: Resultsmentioning

confidence: 99%

Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells

Wise

Duhachek-Muggy

et al. 2016

Breast Cancer Res Treat

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“…For example, PI3K is mutated in the SUM159 cell line (H1047L mutation) but not in the MDA-MB-231 cells [32]. The SUM159 cells also express mutant Hras [33]. Interestingly, tumor growth acceleration by Notch2 knockdown is relatively more pronounced in the MDA-MB-231 cells compared with SUM159.…”

Section: Discussionmentioning

confidence: 99%

Withaferin A inhibits in vivo growth of breast cancer cells accelerated by Notch2 knockdown

Kim

Hahm

Arlotti

et al. 2016

Breast Cancer Res Treat

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Purpose The present study offers novel insights into the molecular circuitry of accelerated in vivo tumor growth by Notch2 knockdown in triple-negative breast cancer (TNBC) cells. Therapeutic vulnerability of Notch2-altered growth to a small molecule (withaferin A; WA) is also demonstrated. Methods MDA-MB-231 and SUM159 cells were used for the xenograft studies. A variety of technologies were deployed to elucidate the mechanisms underlying tumor growth augmentation by Notch2 knockdown and its reversal by WA, including Fluorescence Molecular Tomography for measurement of tumor angiogenesis in live mice, Seahorse Flux analyzer for ex vivo measurement of tumor metabolism, proteomics, and Luminex-based cytokine profiling. Results Stable knockdown of Notch2 resulted in accelerated in vivo tumor growth in both cells reflected by tumor volume and/or latency. For example, the wet tumor weight from mice bearing Notch2 knockdown MDA-MB-231 cells was about 7.1-fold higher compared with control (P < 0.0001). Accelerated tumor growth by Notch2 knockdown was highly sensitive to inhibition by a promising steroidal lactone (WA) derived from a medicinal plant. Molecular underpinnings for tumor growth intensification by Notch2 knockdown included compensatory increase in Notch1 activation, increased cellular proliferation and/or angiogenesis, and increased plasma or tumor levels of growth stimulatory cytokines. WA administration reversed many of these effects providing explanation for its remarkable anti-cancer efficacy. Conclusions Notch2 functions as a tumor growth suppressor in TNBC and WA offers a novel therapeutic strategy for restoring this function.

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“… a Reported in COSMIC database (http://cancer.sanger.ac.uk, (64)) b Reported in (50) and (65) c Reported in (66) N.D., not determined …”

Section: Figurementioning

confidence: 99%

Oncogenic PI3K promotes methionine dependency in breast cancer cells through the cystine-glutamate antiporter xCT

et al. 2017

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The precursor homocysteine is metabolized either through the methionine cycle to produce methionine or through the transsulfuration pathway to synthesize cysteine. Alternatively, cysteine can be obtained through uptake of its oxidized form, cystine. Many cancer cells exhibit methionine dependency such that their proliferation is impaired in growth media in which methionine is replaced by homocysteine. Here, we showed that oncogenic PIK3CA and decreased expression of SLC7A11, a gene that encodes a cystine transporter also known as xCT, correlated with increased methionine dependency in breast cancer cells. Oncogenic PIK3CA was sufficient to confer methionine dependency to mammary epithelial cells, in part by decreasing cystine uptake through the transcriptional and posttranslational inhibition of xCT. Manipulation of xCT activity altered the proliferation of breast cancer cells in methionine-deficient, homocysteine-containing media, suggesting that it functionally contributed to methionine dependency. We propose that concurrent with decreased cystine uptake through xCT, PIK3CA mutant cells use homocysteine through the transsulfuration pathway to synthesize cysteine. Consequently, less homocysteine is available to produce methionine, contributing to methionine dependency. These results indicate that oncogenic PIK3CA alters methionine and cysteine utilization, in part by inhibiting xCT, to contribute to the methionine dependency phenotype in breast cancer cells.

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Phenotypic and Molecular Characterization of MCF10DCIS and SUM Breast Cancer Cell Lines

Cited by 59 publications

References 99 publications

Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells

Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells

Withaferin A inhibits in vivo growth of breast cancer cells accelerated by Notch2 knockdown

Oncogenic PI3K promotes methionine dependency in breast cancer cells through the cystine-glutamate antiporter xCT

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