The substrate domain of BCAR1 is essential for anti-estrogen-resistant proliferation of human breast cancer cells.

To unravel the mechanisms underlying failure of endocrine therapy of breast cancer, we have previously executed a functional genetic screen and identified the adaptor protein BCAR1 to be causative for tamoxifen resistance. As a consequence of the manifold of interactions with other proteins, we characterized the contribution of individual protein domains of BCAR1 to anti-estrogen-resistant proliferation of human breast cancer cells. We took advantage of the observation that the closely related family member HEF1 was unable to support long-term anti-estrogen-resistant cell proliferation.

Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway.

Introduction: Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known.

The prognostic value of BCAR1 in patients with primary breast cancer.

Purpose: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large series of breast cancer specimens.

Experimental Design: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols.

Development of an ELISA for measurement of BCAR1 protein in human breast cancer tissue.

Background: High concentrations of breast cancer anti-estrogen resistance 1 (BCAR1) protein measured by Western blotting in primary breast tumor cytosols are associated with early disease progression and failure of tamoxifen therapy. The aim of the present study was to develop an ELISA to measure BCAR1 quantitatively in extracts of human breast cancer tissue.

Methods: A recombinant fragment of BCAR1 (the human homolog of murine p130Cas) was produced in bacterial M15 cells, purified, and injected into chickens and rabbits.