Coactivators in the diagnosis and treatment of breast cancer

Details Coactivators in the diagnosis and treatment of breast cancer Coactivators in the diagnosis and treatment of breast cancer

2007-10-16

2007-10-16

Foley, Shanon (Department: 1642)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C536S023500, C435S252300, C435S320100

Reexamination Certificate

active

10751113

ABSTRACT:
This invention relates to the AIB1 protein as a coactivator that potentiates the transcriptional activity of nuclear hormone receptors. The gene is amplified in a subset of human breast cancers. One splice variant of AIB1 transcribes a mRNA that lacks the exon 3 sequence. Δ3-AIB1 mRNA encodes a 130 kDa protein that lacks the N-terminal basic helix-loop-helix and a portion of the PAS dimerization domain. This 130 kDa protein was detected 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. The abundance of Δ3-AIB1 mRNA is increased in human breast cancer specimens relative to that in normal breast tissue. Functional reporter gene assays revealed that the ability of Δ3-AIB1 to promote transcription mediated by the estrogen or progesterone receptors was significantly greater than that of the full-length protein. The Δ3-AIB1 isoform was also more effective than AIB1 in promoting transcription induced by epidermal growth factor. Thus, over expression of Δ3-AIB1 plays an important role in sensitizing breast tumor cells to hormone or growth factor stimulation.

REFERENCES:
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Wang, Zhlyong et al., “Regulation of Somatic Growth by the p160 Coactive p/CIP,”PNAS, 97(25): 13549-13554 (2000).
Reiter, Ronald et al., “An Isoform of the Coactivator AIB1 That Increases Hormone and Growth Factor Sensitivity is Overexpressed in Breast Cancer,”Journal of Biological Chemistry, 276(43):39736-39741 (2001).

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