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目的筛选乳腺癌中长脾脏酪氨酸激酶[Syk(L)]作为转录抑制因子下调的靶基因,探讨 Syk(L)在乳腺癌中的抑癌机制。方法采用 CLONTECH 公司的 Adeno-X~(TM)表达系统构建 Syk的腺病毒载体,感染不表达 Syk 的乳腺癌细胞系 MB231,以腺病毒 LacZ 作为对照,采用 cDNA 微阵列方法筛选 Syk(L)、Syk(S)调节的基因 ID1、Cyclin D1、Fral 和 B-myb 的表达;并采用 Northern 杂交的方法验证 cDNA 微阵列结果。结果在乳腺癌细胞中,转录抑制因子 Syk(L)可下调癌基因 ID1、CyclinD1、Fra1和 B-myb 的表达,Northern 杂交证实了 Syk(L)对它们的调节。结论抑癌基因 Syk(L)通过特异性下调癌基因 Cyclin D1、ID1、B-myb 和 Fra1的表达抑制乳腺癌的发展。
Objective To screen the long spleen tyrosine kinase [Syk (L)] in breast cancer as a target gene of down-regulation of transcriptional repressor and to explore the mechanism of Syk (L) suppression in breast cancer. Methods Adeno-X ~ (TM) expression system of CLONTECH was used to construct the adenovirus vector of Syk and to infect Syk-deficient breast cancer cell line MB231. The adenovirus LacZ was used as a control to screen Syk (L) Syk (S) regulated the expression of ID1, Cyclin D1, Fral and B-myb. The results of cDNA microarray were verified by Northern blot. Results Syk (L), a transcriptional repressor, can down-regulate the expression of oncogenes ID1, CyclinD1, Fra1 and B-myb in breast cancer cells. Northern blotting confirmed that Syk (L) regulates them. Conclusions The tumor suppressor gene Syk (L) inhibits the development of breast cancer by downregulating the expression of the oncogenes Cyclin D1, ID1, B-myb and Fra1.