Overexpression of KAI1 suppresses in vitro invasiveness and in vivo metastasis in breast cancer cells.
Overexpression of KAI1 suppresses in vitro invasiveness and in vivo metastasis in breast cancer cells.
复制标题
DOI：
--
复制
发表时间：
2001-07
期刊：
影响因子：
11.2
通讯作者：
Xiaohong Yang;L. Wei;Careen K. Tang;Rebecca Slack;S. Mueller;M. Lippman
中科院分区：
文献类型：
--
作者：
Xiaohong Yang;L. Wei;Careen K. Tang;Rebecca Slack;S. Mueller;M. Lippman
KAI1是人类前列腺癌的转移抑制基因，也参与了其他多种人类癌症的进展。此前，我们已经证明KAI1在转移性乳腺癌细胞系和高侵袭性乳腺癌标本中表达下调。为了确定KAI1的表达是否与乳腺癌的转移抑制有关，我们将人KAI1基因导入两个高度恶性的乳腺癌细胞株LCC6和MDA-MB-231，这两个细胞株都有低水平的内源性KAI1表达。将亲本、纯载体和KAI1转基因克隆分别注射到裸鼠的乳房脂肪垫和尾静脉中，评估其自发性和实验性肺转移。KAI1的高表达显著抑制了KAI1基因转导的LCC6细胞的转移潜能。转移抑制与肿瘤生长速度降低和软琼脂克隆形成能力降低有关。此外，KAI1的表达显著抑制了KAI1转基因的MDA-MB-231细胞的体外侵袭能力。我们的结果提示KAI1可能是乳腺癌转移的负调控因子。
KAI1 is a metastasis suppressor gene for human prostate cancer and is also involved in the progression of a variety of other human cancers. Previously, we have demonstrated that KAI1 expression was down-regulated in metastatic breast cancer cell lines as well as in highly aggressive breast cancer specimens. To determine whether KAI1 expression is responsible for the metastasis suppression in breast cancer, we transfected the human KAI1 cDNA into two highly malignant breast cancer cell lines, LCC6 and MDA-MB-231, which both have low levels of endogenous KAI1 expression. Parental, vector-only transfectants and KAI1 transfectant clones were injected into the mammary fat pads and tail veins, respectively, of athymic nude mice and assessed for both spontaneous and experimental lung metastasis. High KAI1 expression significantly suppressed the metastatic potential of KAI1-transfected LCC6 cells. Metastasis suppression correlated with the reduced rate of tumor growth and a decreased clonogenicity in soft agar. Furthermore, KAI1 expression significantly suppressed the in vitro cell invasion in KAI1-transfected MDA-MB-231 cells. Our results suggested that KAI1 may function as a negative regulator of breast cancer metastasis.