Investigation of Alpha6 Integrins and Their Signaling Intermediates as Prognostic Markets for Breast Cancer
Annual summary rept. 1 Msy 2001-30 Apr 2003
M D ANDERSON CANCER CENTER HOUSTON TX
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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.
- Medicine and Medical Research