Expression of the WAVE (WASP Verprolin-homologous) molecules in human breast cancer

Abstract

21061 Background: WAVEs (WASP Verprolin-homologous) belongs to the CCN family which comprises of nine members, the cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2) and nephroblastoma over-expressed (Nov/CCN3), Wnt-induced secreted proteins(WISPs)1, 2 and 3 (CCN4–6) as well as the WAVE-1,2 and 3 (also known as CCN7–9 respectively). Some members of the CCN family, such as Cyr61 and CTGF are known to stimulate mitosis, adhesion, apoptosis, extracellular matrix production, cell migration and growth arrest in cancer cells including breast cancer cells. However, there is no knowledge of the expression pattern and the function of WAVEs in human breast cancer. Here, we report the expression of WAVE-1,-2 and -3 transcripts and proteins in relation to clinical and pathological characteristics in human breast cancer. Methods: The expression of the three WAVE molecules at the mRNA and protein levels in a cohort of 122 human breast cancers and 32 normal breast tissues were analysed and correlated with the patients’ clinical outcome. The respective transcripts were quantitative determined using real time RT-PCR and distribution of the proteins were investigated by immunohistochemical methods. Results: All three WAVE proteins were detected in mammary epithelial cells and are of cytoplasmic nature. Breast cancer cells from the tissues also displayed positive staining of the WAVE proteins, with WAVE-2 staining appears weaker compared with normal epithelial cells. WAVE-1 transcripts were expressed in significantly high levels (p=0.03) in high grade breast cancers. Low levels of WAVE-2 were associated with higher TNM staging (p=0.038 in TNM3 and p=0.017 in TNM4) and were also found in patients with poor prognosis. Interesting, a marginal reduction of WAVE-3 transcripts was seen in patients who developed systemic metastasis. No other significant associations were found between the WAVE1 and WAVE3 transcripts and the breast cancer cells. Conclusions: WAVEs are widely expressed in human mammary tissues and have a differential expression in human breast cancer with WAVE2 appearing to be associated with the aggressiveness of breast tumors. No significant financial relationships to disclose.