Coactivators in the Diagnosis and Treatment of Breast Cancer

Categories: "Cancer Therapeutics"

Reference #: 2001-022

OTC Contact: Ruchika Nijhara, Ph.D., MBA, CLP (Directory Information | Send a Message)

Description

The AIB1 gene encodes a coactivator that potentiates the transcriptional activity of nuclear hormone receptor, and is amplified in subset of breast cancer. One splice variant of AIB1 transcribes a mRNA that lacks the exon 3 sequence, and the encoded protein was found to be present in MCF-7 breast cancer cells at levels 5-10% of the full length protein. Whereas in non transformed mammary epithelium lines the Δ3-AIB1 protein is present at significantly lower levels compared to the full length AIB1. Specifically, the present invention is directed to isolated nucleic sequences that encode the isoform Δ3-AIB1. The invention further encompasses vectors that contain the nucleic acid of isoform of the invention, and also recombinant cells, which may be either eukaryotic or prokaryotic, containing nucleic acids or vectors of the invention.

Applications

  • As a prognostic and diagnostic marker for breast cancer.
  • Can be used as a sensitive indicator for the progression of cancer to a more hormone-independent phenotype
  • Developing screening assays to identify inhibitors for AIB1-Δ3
  • Research tool

Advantages

  • Per molecule basis, Δ3-AIB1 is more potent transcriptional coactivator of steroid receptors, and also for growth factor signaling than the full-length protein.
  • Δ3-AIB1 protein is present at much lower level compared to full length protein in normal cells.

Stage of Development

Studies done to confirm the overexpression of the slice variant in breast cancer cell lines and tissue. Further, the data indicates that over expression of relatively low levels of AIB1-Δ3 isoform can sensitize cells to estrogen, progesterone and growth factors.

Relevant Publications

  • “Overexpression of an N-terminally truncated isoform of the nuclear receptor coactivator amplified in breast cancer 1 leads to altered proliferation of mammary epithelial cells in transgenic mice”. Riegel et al; Mol Endocrinol. 2005 Mar;19(3):644-56.
  • "An Isoform of the Coactivator AIB1 That Increases Hormone and Growth Factor Sensitivity is Overexpressed in Breast Cancer,” Reiter, Ronald et al., Journal of Biological Chemistry, 276(43):39736-39741 (2001).

Inventors

Anna T. Riegel, Ronald Reiter, and Anton Wellstein

Patent Status

US patent #7,282,576 issued on October 16, 2007.