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Isogenic normal basal and luminal mammary epithelial isolated by a novel method show a differential response to ionizing radiation.

Publication ,  Journal Article
Huper, G; Marks, JR
Published in: Cancer Res
April 1, 2007

Epithelial cells within the normal breast duct seem to be the primary target for neoplastic transformation events that eventually produce breast cancer. Normal epithelial cells are easily isolated and propagated using standard techniques. However, these techniques almost invariably result in populations of cells that are largely basal in character. Because only approximately 20% of human breast cancers exhibit a basal phenotype, our understanding of the disease may be skewed by using these cells as the primary comparator to cancer. Further, because germ line mutations in BRCA1 yield breast cancers that are most often of the basal type, a comparison of normal basal and luminal cells could yield insight into the tissue and cell type specificity of this hereditary cancer susceptibility gene. In this report, we describe a simplified and efficient method for isolating basal and luminal cells from normal human breast tissue. These isogenic cells can be independently propagated and maintain phenotypic markers consistent with their respective lineages. Using these cultured cells, we show that basal and luminal cells exhibit distinct responses to ionizing radiation. Basal cells undergo a rapid but labile cell cycle arrest, whereas luminal cells show a much more durable arrest, primarily at the G(2)-M boundary. Molecular markers, including p53 protein accumulation, p53-activated genes, and BRCA1 nuclear focus formation all correlate with the respective cell cycle responses. Further, we show that short-term cultures of human breast tissue fragments treated with ionizing radiation show a similar phenomenon as indicated by the biphasic accumulation of p53 protein in the basal versus luminal layer. Together, these results indicate that normal basal cells have a transitory cell cycle arrest after DNA damage that may underlie their increased susceptibility to transformation after the loss of functional BRCA1.

Duke Scholars

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

April 1, 2007

Volume

67

Issue

7

Start / End Page

2990 / 3001

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Organ Culture Techniques
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Humans
  • Genetic Predisposition to Disease
  • Genes, BRCA1
  • Female
  • Epithelial Cells
  • DNA Damage
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huper, G., & Marks, J. R. (2007). Isogenic normal basal and luminal mammary epithelial isolated by a novel method show a differential response to ionizing radiation. Cancer Res, 67(7), 2990–3001. https://doi.org/10.1158/0008-5472.CAN-06-4065
Huper, Gudrun, and Jeffrey R. Marks. “Isogenic normal basal and luminal mammary epithelial isolated by a novel method show a differential response to ionizing radiation.Cancer Res 67, no. 7 (April 1, 2007): 2990–3001. https://doi.org/10.1158/0008-5472.CAN-06-4065.
Huper, Gudrun, and Jeffrey R. Marks. “Isogenic normal basal and luminal mammary epithelial isolated by a novel method show a differential response to ionizing radiation.Cancer Res, vol. 67, no. 7, Apr. 2007, pp. 2990–3001. Pubmed, doi:10.1158/0008-5472.CAN-06-4065.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

April 1, 2007

Volume

67

Issue

7

Start / End Page

2990 / 3001

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Organ Culture Techniques
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Humans
  • Genetic Predisposition to Disease
  • Genes, BRCA1
  • Female
  • Epithelial Cells
  • DNA Damage