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Thymic model for examining BRCA2 expression and function.

Publication ,  Journal Article
Flores, KG; McAllister, KA; Greer, PK; Wiseman, RW; Hale, LP
Published in: Mol Carcinog
November 2002

Mutations in the human BRCA2 breast cancer susceptibility gene are associated with increased risks of breast, ovarian, and other cancers. BRCA2 has been hypothesized to function in processes of DNA damage/breakage repair, cell proliferation, and apoptosis. These processes continually occur in the thymus during thymocyte development, and BRCA2 mRNA is highly expressed in thymus relative to most other organs. We therefore used the thymus as a model system to study BRCA2 expression and function. Quantitative reverse transcription polymerase chain reaction experiments showed that highly activated immature CD4(+) CD8(+) double-positive human thymocytes that exhibited high levels of proliferation and apoptosis had increased BRCA2 mRNA levels relative to other thymocyte subsets. BRCA2 mRNA levels were upregulated in thymocytes treated with the DNA-damaging agent etoposide. Only modest increases were associated with proliferation in human peripheral lymphocytes in response to concanavalin A (ConA) mitogen. Mice homozygous for a targeted mutation in Brca2 exon 27 (Brca2(Delta27/Delta27)) showed normal thymic architecture but had 18% decreased thymocyte cellularity compared with wild-type mice. Thymocytes from these Brca2(Delta27/Delta27) mice displayed decreased apoptosis in response to etoposide-induced DNA damage compared with wild-type thymocytes. These studies suggest that BRCA2 mRNA levels are modulated during DNA damage and may be important during apoptosis.

Duke Scholars

Published In

Mol Carcinog

DOI

ISSN

0899-1987

Publication Date

November 2002

Volume

35

Issue

3

Start / End Page

103 / 109

Location

United States

Related Subject Headings

  • Up-Regulation
  • Thymus Gland
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Female
  • Etoposide
 

Citation

APA
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ICMJE
MLA
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Flores, K. G., McAllister, K. A., Greer, P. K., Wiseman, R. W., & Hale, L. P. (2002). Thymic model for examining BRCA2 expression and function. Mol Carcinog, 35(3), 103–109. https://doi.org/10.1002/mc.10081
Flores, Kristina G., Kimberly A. McAllister, Paula K. Greer, Roger W. Wiseman, and Laura P. Hale. “Thymic model for examining BRCA2 expression and function.Mol Carcinog 35, no. 3 (November 2002): 103–9. https://doi.org/10.1002/mc.10081.
Flores KG, McAllister KA, Greer PK, Wiseman RW, Hale LP. Thymic model for examining BRCA2 expression and function. Mol Carcinog. 2002 Nov;35(3):103–9.
Flores, Kristina G., et al. “Thymic model for examining BRCA2 expression and function.Mol Carcinog, vol. 35, no. 3, Nov. 2002, pp. 103–09. Pubmed, doi:10.1002/mc.10081.
Flores KG, McAllister KA, Greer PK, Wiseman RW, Hale LP. Thymic model for examining BRCA2 expression and function. Mol Carcinog. 2002 Nov;35(3):103–109.
Journal cover image

Published In

Mol Carcinog

DOI

ISSN

0899-1987

Publication Date

November 2002

Volume

35

Issue

3

Start / End Page

103 / 109

Location

United States

Related Subject Headings

  • Up-Regulation
  • Thymus Gland
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Female
  • Etoposide