Retinoic acid receptor beta2 inhibition of metastasis in mouse mammary gland xenografts.
Retinoic acid receptor beta2 inhibition of metastasis in mouse mammary gland xenografts.
复制标题
视黄酸受体β2抑制小鼠乳腺异种移植物的转移。
DOI：
10.1023/a:1014906529407
复制
发表时间：
2002
影响因子：
3.8
通讯作者：
Swisshelm,Karen
中科院分区：
文献类型：
--
作者：
Treuting,PiperM;Chen,LucindaI;Buetow,BernardS;Zeng,Weiping;Birkebak,TedA;Seewaldt,VictoriaL;Sommer,KarenM;Emond,Mary;Maggio-Price,Lillian;Swisshelm,Karen
The retinoic acid receptor β2(RARβ2) protein is a putative tumor suppressor that inhibits proliferation and can induce apoptosis when introduced into breast, cervical, lung, and pancreatic cancer cell lines. To determine if RARβ2suppresses proliferation of mammary-derived cancer cellsin vivo, we transduced MDA-MB-435 breast cancer cells with the LXSN retroviral vector containing RARβ2and implanted LXSN vector- or RARβ2-transduced cells into the mammary fat pads of nude and severe combined immune deficiency (SCID) mice. We analyzed the xenografts for several tumor parameters, including tumor size, inflammation, vascularity, mitoses, tumor recurrence at the primary site following resection, and metastases. We found that 19 of 52 mice inoculated with vector-transduced cells developed metastases in multiple organs while only one of 55 mice receiving RARβ2-transduced cells displayed evidence of metastases (p< 0.000001, combined experiments, two-tailed Fisher's exact test). Moreover, RARβ2-tumor cell recipient mice had a lower incidence of post-resection tumor recurrence (8/55 vs. 25/52,p= 0.0004), 34% less necrosis (in three of four experiments,p= 0.001), and 39% fewer mitoses in tumor tissue (p< 0.000001). Our findings suggest that RARβ2may play a role in inhibiting the metastatic cascade in a mouse mammary gland xenograft tumor model and is a potential candidate for therapeutic intervention in human breast cancer.
