Construction and characterization of recombinant adenoviruses expressing human brca1 or murine brca1 genes

ABSTRACT Recombinant adenoviruses expressing human _BRCA1_ (Ad_BRCA1_), murine _Brca1_ (Ad_Brca1_), three clinically relevant human mutant BRCA1 proteins (t340, C61G, and 1853Stop), or a

murine _Brca1_ C-terminal deletion mutant were constructed and evaluated _in vitro_. These recombinants were capable of transducing high-level transgene expression to a wide variety of cell

lines _in vitro_. Three independent methods were utilized to monitor cell growth following transduction with these recombinants. High-level expression of either the human or mouse wild-type

BRCA1 protein was incompatible with maximal levels of cell growth. Ad_BRCA1_ transduction inhibited the outgrowth of several human breast and ovarian cell lines in colony formation assays.

Flow cytometric analysis revealed an accumulation of the transduced cells in the G0/G1 phase of the cell cycle. This _BRCA1_-mediated accumulation of cells in G0/G1 was accompanied by an

increase in the cellular level of hypophosphorylated pRB. Ad mutant _BRCA1 t340_, _C61G_, and _1853Stop_ viruses were impaired, to varying degrees, in their ability to transduce a

growth-arrested state to the target cells. Using these same three criteria, overexpression of murine _Brca1_ by Ad_Brca1_ was also capable of transducing a growth-arrested state to human

cells. Deletion of the C-terminus of _Brca1_ diminished this activity. This panel of adenoviruses may be useful reagents as part of an approach to understand the function of _BRCA1/Brca1_ in

normal breast and ovary and help to define the tumor suppressor defect (s) conferred by clinical _BRCA1_ mutations in breast and ovarian cell tumorigenesis. CANCER GENE THERAPY (2001) 8,

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Article Open access 17 April 2025 AUTHOR INFORMATION Author notes * Roy A Jensen: Also corresponding author. Roy A Jensen, TVC 4918, Nashville, TN 37232. E-mail:

[email protected] AUTHORS AND AFFILIATIONS * Department of Pathology, Vanderbilt University Medical Center, Nashville, 37232, Tennessee Mel Campbell, Riet van der Meer, 

Randall L Woltjer, Cindy J Yee & Roy A Jensen * Division of Clinical Sciences, Section of Molecular Signaling and Oncogenesis, National Cancer Institute, Bethesda, 20892, Maryland Olga N

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CORRESPONDING AUTHOR Correspondence to Mel Campbell. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Campbell, M., Aprelikova, O., van der Meer, R. _et

al._ Construction and characterization of recombinant adenoviruses expressing human _BRCA1_ or murine _Brca1_ genes. _Cancer Gene Ther_ 8, 231–239 (2001).

https://doi.org/10.1038/sj.cgt.7700291 Download citation * Published: 02 May 2001 * Issue Date: 01 March 2001 * DOI: https://doi.org/10.1038/sj.cgt.7700291 SHARE THIS ARTICLE Anyone you

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Springer Nature SharedIt content-sharing initiative KEYWORDS * Adenoviruses * growth inhibition * cell cycle * tumor suppressor