In vitro assessment of the inflammatory breast cancer cell line SUM 149

Discovery of 2 single nucleotidepolymorphisms in the Rnase L gene

Brandon T. Nokes, Heather E. Cunliffe, Bonnie LaFleur, David W. Mount, Robert B Livingston, Bernard W Futscher, Julie E. Lang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Inflammatory breast cancer (IBC) is a rare, highly aggressive form of breast cancer. The mechanism of IBC carcinogenesis remains unknown. We sought to evaluate potential genetic risk factors for IBC and whether or not the IBC cell lines SUM149 and SUM190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We evaluated dose-response to treatment with interferon- alpha (IFN-a); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated in IBC) in SUM149 cells. A bioinformatic analysis was performed to evaluate expression of RNase L in IBC and non-IBC. Results: 2 of 2 IBC cell lines were homozygous for RNase L common missense variants 462 and 541; whereas 2 of 10 non-IBC cell lines were homozygous positive for the 462 variant (p= 0.09) and 0 of 10 non-IBC cell lines were homozygous positive for the 541 variant (p = 0.015). Our real-time polymerase chain reaction (RT-PCR) and Southern blot analysis for sequences of HMTV revealed no evidence of the putative viral genome. Conclusion: We discovered 2 SNPs in the RNase L gene that were homozygously present in IBC cell lines. The 462 variant was absent in non-IBC lines. Our discovery of these SNPs present in IBC cell lines suggests a possible biomarker for risk of IBC. We found no evidence of HMTV in SUM149 cells. A query of a panel of human IBC and non-IBC samples showed no difference in RNase L expression. Further studies of the RNase L 462 and 541 variants in IBC tissues are warranted to validate our in vitro findings.

Original languageEnglish (US)
Pages (from-to)104-116
Number of pages13
JournalJournal of Cancer
Volume4
Issue number2
DOIs
StatePublished - 2013

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Inflammatory Breast Neoplasms
Cell Line
Ribonucleases
Genes
Breast Neoplasms
Single Nucleotide Polymorphism
In Vitro Techniques
2-5A-dependent ribonuclease
Oncogenic Viruses
Viral Genome
Virus Diseases
Southern Blotting
Computational Biology
Interferon-alpha
Sequence Analysis

ASJC Scopus subject areas

  • Oncology

Cite this

In vitro assessment of the inflammatory breast cancer cell line SUM 149 : Discovery of 2 single nucleotidepolymorphisms in the Rnase L gene. / Nokes, Brandon T.; Cunliffe, Heather E.; LaFleur, Bonnie; Mount, David W.; Livingston, Robert B; Futscher, Bernard W; Lang, Julie E.

In: Journal of Cancer, Vol. 4, No. 2, 2013, p. 104-116.

Research output: Contribution to journalArticle

Nokes, Brandon T. ; Cunliffe, Heather E. ; LaFleur, Bonnie ; Mount, David W. ; Livingston, Robert B ; Futscher, Bernard W ; Lang, Julie E. / In vitro assessment of the inflammatory breast cancer cell line SUM 149 : Discovery of 2 single nucleotidepolymorphisms in the Rnase L gene. In: Journal of Cancer. 2013 ; Vol. 4, No. 2. pp. 104-116.
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abstract = "Background: Inflammatory breast cancer (IBC) is a rare, highly aggressive form of breast cancer. The mechanism of IBC carcinogenesis remains unknown. We sought to evaluate potential genetic risk factors for IBC and whether or not the IBC cell lines SUM149 and SUM190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We evaluated dose-response to treatment with interferon- alpha (IFN-a); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated in IBC) in SUM149 cells. A bioinformatic analysis was performed to evaluate expression of RNase L in IBC and non-IBC. Results: 2 of 2 IBC cell lines were homozygous for RNase L common missense variants 462 and 541; whereas 2 of 10 non-IBC cell lines were homozygous positive for the 462 variant (p= 0.09) and 0 of 10 non-IBC cell lines were homozygous positive for the 541 variant (p = 0.015). Our real-time polymerase chain reaction (RT-PCR) and Southern blot analysis for sequences of HMTV revealed no evidence of the putative viral genome. Conclusion: We discovered 2 SNPs in the RNase L gene that were homozygously present in IBC cell lines. The 462 variant was absent in non-IBC lines. Our discovery of these SNPs present in IBC cell lines suggests a possible biomarker for risk of IBC. We found no evidence of HMTV in SUM149 cells. A query of a panel of human IBC and non-IBC samples showed no difference in RNase L expression. Further studies of the RNase L 462 and 541 variants in IBC tissues are warranted to validate our in vitro findings.",
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