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Long-term BRCA1 down-regulation by small hairpin RNAs targeting the 3 ' untranslated region

  1. Author:
    Vondruskova, E.
    Malik, R.
    Sevcik, J.
    Kleiblova, P.
    Kleibl, Z.

  2. Author Address

    Vondruskova, E.; Sevcik, J.; Kleiblova, P.; Kleibl, Z.] Charles Univ Prague, Inst Biochem & Ecpt Oncol, Prague, Czech Republic. [Malik, R.] Charles Univ Prague, Dept Gynaecol & Obstet, Fac Med 1, Prague, Czech Republic. [Kleiblova, P.] Natl Canc Inst, Eukaryotic Transcript Regulat Sect, Lab Prot Dynam & Signaling, Frederick, MD USA.
    1. Year: 2008
  2. Journal: Neoplasma
    1. 55
    2. 2
    3. Pages: 130-137
  4. Type of Article: Article
  1. Abstract:

    Mutations in the BRAC1 gene are responsible for the majority of hereditary breast/ovarian cancers. The functional significance of many mutations/splicing variants identified during the screening of high-risk individuals is difficult to predict due to the lack of in vitro functional tests correlating sequence variants with a risk of cancer development. RNA interference is a promising tool in analyzing functional properties of BRCA1 mutations. Here we designed and functionally analyzed shRNAs directed to 3'-UTR of BRCA1 mRNA that may be used to knock-down expression of endogenous BRCA1. Using retroviral infection, we achieved long-term down-regulation of BRCA1 in a cell-type specific manner. We propose that 3'-UTR-directed shRNAs, coupled with up-regulation of exogenous mutated BRCA1 variants, may constitute a versatile system for the functional analysis of BRCA1 gene alterations.

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External Sources

  1. PMID: 18237251

Library Notes

  1. No notes added.
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