Expression and function of CD9 in melanoma cells.

Expression and function of CD9 in melanoma cells.
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DOI:
10.1002/mc.20580
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发表时间:
2010-01
影响因子:
4.6
通讯作者:
Niles, Richard M.
Niles, Richard M.
中科院分区:
医学2区
文献类型:
--
作者:
Fan, Jun;Zhu, Guo-Zhang;Niles, Richard M.

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CD 9是四跨膜蛋白家族的成员,通过与其他细胞粘附分子相互作用,在四跨膜蛋白网中起组织者的作用。它在分化、受精和细胞迁移中起作用。我们研究了CD 9在黑色素瘤中的表达和功能。与正常黑素细胞相比,B16小鼠黑色素瘤和6个人黑色素瘤细胞系中的CD 9蛋白表达降低。稳定过表达CD 9的B16 F1克隆在软琼脂中形成集落的能力降低;然而矛盾的是,这些过表达克隆侵入基质胶的能力增加。类似地,在人转移性黑素瘤细胞系WM 9中CD 9的瞬时过表达显著降低了锚定非依赖性生长,而在放射状生长期细胞系SbCl 2中CD 9的瞬时过表达导致基质胶侵袭活性的获得。所有6个人黑素瘤细胞系的CD 9 cDNA的DNA测序均未显示缺失、插入或突变。用组蛋白去乙酰化酶抑制剂阿司他汀A治疗所有六种人黑素瘤细胞系增加了CD 9水平。DNA甲基化抑制剂5-氮杂胞苷也增加了CD 9蛋白水平,在来自更恶性的黑色素瘤的细胞系中观察到更大的增加。
CD9, a member of the tetraspanin family, functions as an organizer in “tetraspanin webs”, through interacting with other cell adhesion molecules. It plays a role in differentiation, fertilization and cell migration. We investigated the expression and function of CD9 in melanoma. CD9 protein expression in B16 mouse melanoma and six human melanoma cell lines was decreased compared to normal melanocytes. B16F1 clones stably over-expressing CD9 had reduced ability to form colonies in soft agar; however paradoxically these over-expressing clones had increased ability to invade Matrigel. Similarly, transient over-expression of CD9 in the human metastatic melanoma cell line WM9 dramatically decreased anchorage-independent growth, while transient over-expression of CD9 in the radial growth phase cell line SbCl2 resulted in the gain of Matrigel invasion activity. DNA sequencing of CD9 cDNA from all six human melanoma cell lines did not show deletions, insertions or mutations. Treatment of all six human melanoma cell lines with the histone deacetylase inhibitor trichostatin A increased CD9 levels. The DNA methylation inhibitor 5-aza-cytidine also increased CD9 protein levels with greater increases seen in cell lines derived from more malignant melanomas.
DOI: 10.1084/jem.177.5.1231
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作者:
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