Zia H, Hida T, Jakowlew S, Birrer M, Gozes Y, Reubi J C, Fridkin M, Gozes I, Moody T W
Biomarkers and Prevention Research Branch, National Cancer Institute, Rockville, Maryland 20850, USA.
Cancer Res. 1996 Aug 1;56(15):3486-9.
Breast cancer vasoactive intestinal peptide (VIP) receptors were characterized. Using in vitro autoradiographic techniques, 125I-labeled VIP bound with high affinity to breast biopsy sections. 125I-labeled VIP bound specifically to give breast cancer cell lines examined using receptor-binding techniques. Specific 125I-labeled VIP binding to MDA-MB-231 cells was inhibited with high affinity by VIP and pituitary adenylate cyclase-activating polypeptide (IC50, = 2 nM) and with moderate affinity by the VIP hybrid (IC50 = 0.5 microM). VIP elevated the cAMP in a dose-dependent manner, and VIP hybrid (10 microM) inhibited the increase in cAMP caused by VIP. Using Northern blot analysis, VIP (10 nM) stimulated c-fos and c-myc mRNA, and the increase caused by VIP was reversed by the VIP hybrid. The VIP hybrid inhibited breast cancer growth in vitro and in vivo using nude mice bearing breast cancer xenografts. These data suggest that the VIP hybrid is a breast cancer VIP receptor antagonist.
对乳腺癌血管活性肠肽（VIP）受体进行了特性分析。采用体外放射自显影技术，125I标记的VIP与乳腺癌活检切片具有高亲和力结合。使用受体结合技术检测发现，125I标记的VIP与乳腺癌细胞系特异性结合。VIP和垂体腺苷酸环化酶激活多肽以高亲和力抑制125I标记的VIP与MDA-MB-231细胞的特异性结合（IC50 = 2 nM），VIP杂合体以中等亲和力抑制（IC50 = 0.5 microM）。VIP以剂量依赖性方式升高cAMP，VIP杂合体（10 microM）抑制VIP引起的cAMP增加。采用Northern印迹分析，VIP（10 nM）刺激c-fos和c-myc mRNA，VIP杂合体可逆转VIP引起的增加。使用携带乳腺癌异种移植物的裸鼠，VIP杂合体在体外和体内均抑制乳腺癌生长。这些数据表明，VIP杂合体是一种乳腺癌VIP受体拮抗剂。
