Fornaro M, Tallini G, Bofetiado C J, Bosari S, Languino L R
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Am J Pathol. 1996 Sep;149(3):765-73.
The beta 1C integrin, a member of the cell adhesion receptor superfamily, is an alternatively spliced variant of the beta 1A subunit and, in contrast to its wild-type counterpart, inhibits cell proliferation in vitro. The expression of beta 1C integrin in tumor cell growth was investigated. In benign and neoplastic human prostate tissues, immunohistochemical analysis performed using affinity-purified antibodies specific for beta 1C demonstrated a predominant epithelial expression of beta 1C in benign prostate glands with marked staining of the apical, basal, and lateral surfaces. In the adjacent prostate adenocarcinoma glands, the beta 1C variant was dramatically down-regulated in 27 of 34 (79%) analyzed cases, whereas the expression and distribution of its wild-type counterpart, beta 1A, remained unchanged. Tumors exhibiting different Gleason's patterns showed that beta 1C was down-regulated in comparison with the benign tissue regardless of the histological grade. Immunoblotting analysis, using affinity-purified antibodies specific for beta 1C, was performed, in a quantitative manner, to compare beta 1C expression in benign and tumor prostate tissue. The results showed that beta 1C was expressed in benign prostate tissue whereas it was undetectable in prostate adenocarcinoma. Taken together, these data show that beta 1C integrin down-regulation in prostate tissues correlates with a neoplastic phenotype consistent with its in vitro growth-inhibitory properties. These findings indicate a novel pathophysiological role for this integrin variant in tumorigenesis.
β1C整合素是细胞粘附受体超家族的成员，是β1A亚基的可变剪接变体，与其野生型对应物相反，在体外可抑制细胞增殖。研究了β1C整合素在肿瘤细胞生长中的表达。在良性和肿瘤性人类前列腺组织中，使用针对β1C的亲和纯化抗体进行免疫组织化学分析，结果显示β1C在良性前列腺腺上皮中主要表达，顶端、基底和侧面均有明显染色。在相邻的前列腺腺癌腺管中，34例分析病例中有27例（79%）β1C变体显著下调，而其野生型对应物β1A的表达和分布保持不变。表现出不同Gleason分级模式的肿瘤显示，无论组织学分级如何，与良性组织相比，β1C均下调。使用针对β1C的亲和纯化抗体进行免疫印迹分析，以定量方式比较良性和肿瘤前列腺组织中β1C的表达。结果显示，β1C在良性前列腺组织中表达，而在前列腺腺癌中未检测到。综上所述，这些数据表明前列腺组织中β1C整合素的下调与肿瘤表型相关，与其体外生长抑制特性一致。这些发现表明这种整合素变体在肿瘤发生中具有新的病理生理作用。
