Caveolin-1 inhibits breast cancer growth and metastasis
Caveolin-1 inhibits breast cancer growth and metastasis
复制标题
DOI：
10.1038/sj.onc.1208062
复制
发表时间：
2004-10-14
期刊：
影响因子：
8
通讯作者：
Anderson, RL
中科院分区：
文献类型：
--
作者：
Sloan, EK;Stanley, KL;Anderson, RL
Caveolin-1是在乳腺癌进展相关基因的筛查中发现的。小窝蛋白-1是小窝的主要蛋白质组分，小窝是在许多不同细胞类型中发现的烧瓶状内陷。使用自发性乳腺癌转移的原位模型，发现小窝蛋白-1在低转移性和非转移性原发性肿瘤中表达，但在高转移性4T1.2和4T1.13肿瘤中表达水平低得多。在4T1.2细胞中以中等水平外源表达小窝蛋白-1足以抑制细胞接种到乳腺中后的原发性肿瘤生长。高水平的小窝蛋白-1的表达也抑制了随后向远处器官的转移。表达高水平小窝蛋白-1的细胞表现出侵袭基质胶的能力降低，对层粘连蛋白-1刺激的反应减弱，肺和骨转移减少。这项研究提供了第一个功能证据，小窝蛋白-1调节原发性乳腺肿瘤的生长和乳腺癌的自发转移。
Caveolin-1 was identified in a screen for genes involved in breast cancer progression. Caveolin-1 is the major protein component of caveolae, flask-shaped invaginations found in a number of different cell types. Using an orthotopic model of spontaneous breast cancer metastasis, caveolin-1 was found to be expressed in low and non-metastatic primary tumors, but at much lower levels in highly metastatic 4T1.2 and 4T1.13 tumors. Exogenous expression of caveolin-1 at moderate levels in 4T1.2 cells was sufficient to suppress primary tumor growth after inoculation of cells into the mammary gland. Expression of high levels of caveolin-1 also inhibited subsequent metastasis to distant organs. Cells expressing high levels of caveolin-1 showed reduced capacity to invade Matrigel, diminished response to laminin-1 stimulation and decreased metastasis to lung and bone. This study provides the first functional evidence that caveolin-1 regulates primary breast tumor growth and spontaneous metastasis of breast cancer.