Establishment of two new cell lines derived from human breast carcinomas with HER-2/neu amplification

Meltzer, Paul S.; Leibovitz, Albert; Dalton, WS; Villar, Hugo V.; Kute, Timothy E.; Davis, Joanne; Nagle, Raymond B.; Trent, Jeffrey M.

doi:10.1038/bjc.1991.164

Cited by 49 publications

(31 citation statements)

References 28 publications

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“…Phenotypic changes in response to culture conditions have been reported (Taylor-Papadimitrou et al, 1989) and it is quite likely that genotypic aberrations may be induced with long-term culture. Over the years, new cell lines have been established from only a very small percentage of primary tumours (1-2%; Petersen et al, 1990;Band et al, 1990;Meltzer et al, 1991). However, a more recent report has described the long-term culture of approximately 7% of cultures established from primary breast cancers, nearly all of which went on to form new cell lines (McCallum and Lowther, 1996).…”

Section: Genetic Analysismentioning

confidence: 99%

Short-term primary culture of epithelial cells derived from human breast tumours

Speirs

Green²,

Walton³

et al. 1998

Br J Cancer

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Summary As experimental models for breast cancer, most studies rely on established human breast cancer cell lines. However, many of these lines were established over 20 years ago, many from pleural effusions rather than the primary tumour, so the validity of using them as representative models is questionable. This paper describes our experiences, over a 3-year period, in establishing short-term epithelial-cellenriched preparations from primary breast tumours based on differential centrifugation followed by culture in selective media. Epithelial cells were successfully cultured from 55% of samples, but culture success did not appear to be correlated with tumour histology, stage, grade or node status. Epithelial cell-enriched cultures were immunopositive for broad-spectrum cytokeratin and epithelial membrane antigen (EMA). Positivity for keratin 19 confirmed that the cultures contained tumour-derived cells, which additionally showed significantly higher activity of the reductive pathway of the steroid-converting enzyme 17p-hydroxysteroid dehydrogenase type 1. That the cultures contained tumour and not normal epithelial cells was further substantiated by the complete absence of the calmodulin-like gene NB-1 in tumour-derived cultures; this is only associated with normal breast epithelia. Eighty-five per cent of cultures established from oestrogen receptor (ER)-positive tumours expressed ER in vitro; this was functional in 66% of cultures, although ER-positive phenotype was gradually lost over time. In conclusion, epithelial cells can be isolated and maintained as short-term cultures from primary breast tumours irrespective of histopathological or clinical details, providing a model system with a greater biological and clinical relevance than breast cancer cell lines.

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Section: Genetic Analysismentioning

confidence: 99%

Short-term primary culture of epithelial cells derived from human breast tumours

Speirs

Green²,

Walton³

et al. 1998

Br J Cancer

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“…The early passage sporadic breast cancer cell lines were developed and maintained at the Arizona Cancer Center Cell Culture Core Facility. The UACC1179 and UACC2087 cells were derived from pleural effusions, while UACC893 was derived from a primary tumor (Meltzer et al, 1991;Thompson et al, 1993;Trent et al, 1993). MDA-MB-435 and MDA-MB-231 were maintained in RPMI 1640 containing 5% fetal bovine serum supplemented with 50 mg/ ml pen/strep.…”

Section: Cell Culture Adenoviral Infections and Drug Treatmentsmentioning

confidence: 99%

Mutant p53 and aberrant cytosine methylation cooperate to silence gene expression

et al. 2003

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p53 is an important transcriptional regulator that is frequently mutated in cancer. Gene-profiling experiments of breast cancer cells infected with wt p53 revealed both MASPIN and desmocollin 3 (DSC3) to be p53-target genes, even though both genes are silenced in association with aberrant cytosine methylation of their promoters. Despite the transcriptional repression of these genes by aberrant DNA methylation, restoration of p53 resulted in the partial reactivation of both genes. This reactivation is a result of wt p53 binding to its consensus DNA-binding sites within the MASPIN and DSC3 promoters, stimulating histone acetylation, and enhancing chromatin accessibility of their promoters. Interestingly, wt p53 alone did not affect the methylation status of either promoter, suggesting that p53 itself can partially overcome the repressive barrier of DNA methylation. Pharmacologic inhibition of DNA methylation with 5-aza-2 0 -deoxycytidine in combination with restoration of wt p53 status resulted in a synergistic reactivation of these genes to near-normal levels. These results suggest that cancer treatments that target both genetic and epigenetic facets of gene regulation may be a useful strategy towards the therapeutic transcriptional reprogramming of cancer cells.

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“…In this study, we compared the MnSOD expression at the mRNA, protein and activity levels in the immortalized but nontumorigenic human mammary epithelial cell line MCF-10A and two different tumorigenic human breast carcinoma cell lines, UACC-893 27 and MDA-MB-435. We found a two to three fold lower MnSOD expression in the carcinoma cells than in the non-tumorigenic cells.…”

mentioning

confidence: 99%

Epigenetic Regulation of Manganese Superoxide Dismutase Expression in Human Breast Cancer Cells

Hitchler¹,

Wikainapakul²,

Yu³

et al. 2006

Epigenetics

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Malignant breast cancer cells often exhibit lower expression and activity of manganese superoxide dismutase (MnSOD) than their normal cell counterparts; however, the mechanism(s) responsible for this change remains unclear. We examined whether SOD2, the gene encoding MnSOD, was epigenetically repressed in breast cancer cell lines by DNA methylation and histone acetylation. RT-PCR analysis of SOD2 mRNA showed the nontumorigenic breast epithelial cell line MCF-10A to have two to three fold higher expression levels than either UACC-893 or MDA-MB-435 breast carcinoma cells. Analysis of a region in the SOD2 promoter by sodium bisulfite genomic sequencing demonstrated significantly higher levels of CpG methylation in both human breast carcinoma cell lines assessed than in MCF-10A cells. CREB binding in vitro to a cognate site derived from this region was repressed by DNA methylation, and CREB binding to the 5' regulatory region of the SOD2 gene in vivo as determined by ChIP was significantly lower in breast carcinoma cells than in MCF-10A. Increased cytosine methylation was also accompanied by a significant decrease in the level of acetylated histones in the same region of the SOD2 promoter. Finally, a causal link between cytosine methylation and transcriptional repression was established by increasing MnSOD mRNA, protein and activity in breast carcinoma cells using the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. These findings indicate that epigenetic silencing of SOD2 constitutes one mechanism leading to the decreased expression of MnSOD observed in many breast cancers.

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Establishment of two new cell lines derived from human breast carcinomas with HER-2/neu amplification

Cited by 49 publications

References 28 publications

Short-term primary culture of epithelial cells derived from human breast tumours

Short-term primary culture of epithelial cells derived from human breast tumours

Mutant p53 and aberrant cytosine methylation cooperate to silence gene expression

Epigenetic Regulation of Manganese Superoxide Dismutase Expression in Human Breast Cancer Cells

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