Asch H L, Head K, Dong Y, Natoli F, Winston J S, Connolly J L, Asch B B
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Cancer Res. 1996 Nov 1;56(21):4841-5.
Down-regulation of gelsolin, an actin-binding protein, is frequently found in several types of transformed cells and tumors. The present study demonstrates that gelsolin protein and RNA were absent or markedly reduced in human breast cancer cell lines relative to "normal" mortal human mammary epithelial cells and benign, immortalized cell lines. Moreover, actin filaments were usually attenuated coincident with the reduction in gelsolin. Gelsolin was also missing or greatly decreased in 70% of 30 human sporadic, invasive breast carcinomas examined by immunocytochemistry and in 100% of virally induced mouse and chemically induced rat mammary carcinomas evaluated by Northern analysis. Southern analysis revealed no major mutations in the gelsolin gene of human breast cancer cells. Our results show that partial or total loss of gelsolin expression is common to the majority of breast cancers of diverse etiologies in three animal species and point to gelsolin as a candidate suppressor of breast cancer.
凝溶胶蛋白是一种肌动蛋白结合蛋白，在多种类型的转化细胞和肿瘤中常出现表达下调。本研究表明，相对于“正常”的有限增殖人乳腺上皮细胞和良性永生化细胞系，人乳腺癌细胞系中凝溶胶蛋白的蛋白质和RNA缺失或显著减少。此外，肌动蛋白丝通常会随着凝溶胶蛋白的减少而变细。通过免疫细胞化学检测，在30例人类散发性浸润性乳腺癌中有70%的病例凝溶胶蛋白缺失或大幅减少；通过Northern分析评估，在100%的病毒诱导小鼠乳腺癌和化学诱导大鼠乳腺癌中凝溶胶蛋白也缺失或大幅减少。Southern分析显示人乳腺癌细胞的凝溶胶蛋白基因无重大突变。我们的结果表明，凝溶胶蛋白表达部分或完全缺失在三种动物物种中多种病因的大多数乳腺癌中很常见，这表明凝溶胶蛋白是乳腺癌的一个候选抑制因子。
