干扰素对小鼠乳腺癌细胞侵袭力及转移相关基因表达的调变

Modulation of invasiveness and invasion/metastasis associated gene expression of a mouse mammary adenocarcinoma by interferons

目的研究不同干扰素对肿瘤细胞侵袭力及侵袭转移相关基因表达的调变作用。方法根据细胞穿过铺有Ｍａｔｒｉｇｅｌ胶多孔膜的数量检测细胞侵袭力，用流式细胞分析和Ｎｏｒｔｈｅｒｎ杂交检测细胞表面抗原和ｍＲＮＡ表达水平。结果ＭＡ－８９１细胞经ＩＦＮ－γ处理体外侵袭力明显增强（Ｐ＜０．０１），经ＩＦＮ－α处理侵袭力下降。ＩＦＮ－γ显著增加细胞表面ＩＣＡＭ－１和７２０００ＩＶ型胶原酶表达水平，ＩＦＮ－α不增加细胞ＩＣＡＭ－１的表达但显著上调ｎｍ２３基因的表达水平。结论ＩＦＮ－γ和ＩＦＮ－α对ＭＡ－８９１细胞侵袭转移相关的基因和基因产物表达有不同的作用，而对其转移潜能产生不同的调变作用。

Objective To investigate the effects of IFNs on the in vitro invasiveness and the expression of several genes related to invasion and metastatic behavior of MA 891 cells.Methods The invasiveness was assessed by penetration through a matrigel coated filter. Cell surface antigen and mRNA levels were analyzed by flow cytometry and Northern blot respectively. Results IFN γ pretreatment increased the invasiveness of MA 891 ( P <0 01) Pretreatment with IFN α decreased the invasiveness of cells, but it was not statistically significant. Cell surface ICAM 1 was not found on MA 891 cells even after treatment with IFN α, but was strongly induced after IFN γ treatment. Another adhesion molecule CD44v mRNA, absent on MA 891 cells, could not be induced to express by either IFN. Both 72 000 and 92 000 type IV collagenase mRNAs were detectable in MA 891 cells. The 72kD type IV collagenase expression was up regulated by IFN γ and IFN α, but the levels of expression were significantly higher in cells treated with IFN γ than those treated with IFN α. IFN γ and IFN α treatment had little or no effect on expression of the 92 000 type IV collagenase. Treatment with IFN γ had no effects on antimetastasis nm23 gene expression whereas treatment with IFN α resulted in marked up regulation of its expression.Conclusion IFN γ and IFN α differ in their effects on the expression of genes related to invasion and metastasis of MA 891 cells, thereby differentially modulating metastatic potential.