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BMP9 抑制乳腺癌细胞 MDA-MB-231 的增殖和侵袭。

BMP9 inhibits the proliferation and invasiveness of breast cancer cells MDA-MB-231.

机构信息

Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, 1 YiXueYuan Road, Yuzhong District, Chongqing 400016, China.

出版信息

J Cancer Res Clin Oncol. 2011 Nov;137(11):1687-96. doi: 10.1007/s00432-011-1047-4. Epub 2011 Sep 3.

DOI:10.1007/s00432-011-1047-4
PMID:21892652
Abstract

BACKGROUND

Transforming growth factor-β (TGF-β) is known to promote tumor proliferation, migration, invasion, and metastasis. Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily. Several BMPs (BMP2 and BMP7) can enhance the invasion and bone metastasis of breast cancer cells. The function of BMP9, the latest discovered and most powerful osteogenetic factor, in breast cancer has not been fully elucidated.

METHODS

BMP9 expression in twenty-three breast cancer patients and three breast cancer cell line types was detected by reverse transcriptase polymerase chain reaction. Changes in proliferation, apoptosis, invasion, and migration in the recombinant MDA-MB-231/BMP9 cells were detected using various assays. The assays were MTT, flow cytometry, colony forming, cell wounding, and transwell invasion. Proliferating cell nuclear antigen and terminal deoxynucleotidy transferase biotin-dUTP nick end labeling staining methods were conducted to detect whether BMP9 affected proliferation and apoptosis in xenogenic mouse models.

RESULTS

Twenty-one of the twenty-three breast cancer patients had amplified BMP9 mRNA transcripts in adjacent non-tumor tissues, although BMP9 was observed in the breast cancer tissue of two patients, its expression was higher in the adjacent non-tumor tissues. BMP9 overexpression inhibited the proliferation, migration, and invasion, as well as induced the apoptosis of the breast cancer cell line MDA-MB-231 in vitro. BMP9 also inhibited tumor growth and induced apoptosis significantly in the xenogenic mouse models.

CONCLUSIONS

Decreased BMP9 expression is associated with the elevated proliferation and migration of human breast cancer. BMP9 can inhibit the growth, invasion, and migration of breast cancer cells in vitro and in vivo. BMP9 is a putative tumor suppressor in breast cancer.

摘要

背景

转化生长因子-β(TGF-β)已知可促进肿瘤增殖、迁移、侵袭和转移。骨形态发生蛋白(BMPs)是 TGF-β 超家族的成员。几种 BMPs(BMP2 和 BMP7)可增强乳腺癌细胞的侵袭和骨转移。最新发现的、最强大的成骨因子 BMP9 在乳腺癌中的功能尚未完全阐明。

方法

采用逆转录聚合酶链反应检测 23 例乳腺癌患者和 3 种乳腺癌细胞系中 BMP9 的表达。采用 MTT、流式细胞术、集落形成、细胞划痕和 Transwell 侵袭等检测重组 MDA-MB-231/BMP9 细胞增殖、凋亡、侵袭和迁移的变化。增殖细胞核抗原和末端脱氧核苷酸转移酶生物素-dUTP 缺口末端标记染色法检测 BMP9 是否影响异种小鼠模型中的增殖和凋亡。

结果

23 例乳腺癌患者中有 21 例在邻近非肿瘤组织中扩增 BMP9 mRNA 转录本,尽管有 2 例乳腺癌组织中观察到 BMP9,但在邻近非肿瘤组织中的表达更高。BMP9 过表达抑制乳腺癌细胞系 MDA-MB-231 的体外增殖、迁移和侵袭,并诱导其凋亡。BMP9 还显著抑制异种小鼠模型中的肿瘤生长并诱导其凋亡。

结论

BMP9 表达降低与人类乳腺癌的增殖和迁移增加有关。BMP9 可抑制乳腺癌细胞在体外和体内的生长、侵袭和迁移。BMP9 是乳腺癌中的潜在肿瘤抑制因子。

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