Investigation of Alpha6 Integrins and Their Signaling Intermediates as Prognostic Markets for Breast Cancer

摘要

We are investigating the role of alpha6beta4 integrin expression in the progression of breast cancer. Using an oligonucleotide probe for beta4 integrin mRNA, we evaluated beta4 mRNA expression in a cohort of patients with node-negative invasive breast carcinoma. We found no association between beta4 mRNA expression and 5-year or 10-year disease-free or disease- specific survival. However, we did observe a correlation between beta4 mRNA expression and tumor size, suggesting that alpha6beta4 integrin may nevertheless play a role in tumor progression. One hundred and forty-four invasive breast carcinoma specimens have been collected so far by fine-needle aspiration, surface beta4 has been clustered, cytospin preparations have been prepared, and cell lysates have been prepared and frozen for future Western blot analyses. We evaluated alpha6beta4-mediated signaling in breast carcinoma cell lines, and we observed that clustering of surface J34 results in the PI3K-dependent phosphorylation of nonmuscle myosin IT heavy chain. This may affect actin-myosin filament organization. If changes in actin-myosin filament organization are observed in breast carcinoma cell lines following alpha6beta4 clustering, effects on actin- myosin filament organization will be evaluated subsequently in the breast carcinoma cytospin preparations and correlated with clinical parameters.