Expression profile of tyrosine kinases in breast cancer.
Expression profile of tyrosine kinases in breast cancer.
复制标题
DOI：
--
复制
发表时间：
2002-02
期刊：
影响因子：
--
通讯作者：
F. Meric;Wei‐Ping Lee;A. Sahin;Haixia Zhang;H. Kung;M. Hung
中科院分区：
文献类型：
--
作者：
F. Meric;Wei‐Ping Lee;A. Sahin;Haixia Zhang;H. Kung;M. Hung
酪氨酸激酶（TK）家族包括许多生长因子受体、细胞周期调节因子和癌蛋白。此外，受体TKs HER2/neu和表皮生长因子受体在乳腺肿瘤的一个亚组中过度表达，并与更具攻击性的行为相关。因此，TKs正被积极地作为治疗靶点。本研究的目的是确定乳腺癌中TKs的表达模式。利用基于TKs催化结构域保守基序的简并引物进行逆转录pcr，并通过一组限制性内切酶酶切确定逆转录pcr产物的身份。利用TK显示实验，我们研究了13种乳腺癌细胞系和2种正常永生化乳腺上皮细胞系的TK谱。TK显示试验可重复地证明了HER-2/neu在细胞系之间表达的已知差异。在乳腺癌细胞中检测到几种TKs，包括受体TKs Axl、Cak、成纤维细胞生长因子受体4、HEK8、HER2/neu、c-MET、RET和非受体TKs ARG、BRK、Janus激酶1、Rak和YES。多种激酶在不同细胞系间表达存在差异。使用来自人类乳腺肿瘤的RNA发现了类似的TK谱。我们得出结论，乳腺癌的TK表达模式存在显著的可变性。在选择TK抑制剂治疗患者时应考虑到这种可变性。
The tyrosine kinase (TK) family includes many growth factor receptors, cell cycle regulators, and oncoproteins. Moreover, the receptor TKs HER2/neu and epidermal growth factor receptor are overexpressed in a subgroup of breast tumors and correlate with more aggressive behavior. Thus, TKs are being actively pursued as therapeutic targets. The purpose of this study was to determine the expression pattern of TKs in breast cancer. Reverse transcription-PCR was performed with degenerate primers based on conserved motifs of the catalytic domains of TKs, and the identities of the reverse transcription-PCR products were determined by digestion with a panel of restriction enzymes. Using a TK display assay, we studied the TK profiles of 13 breast cancer cell lines and two normal immortalized breast epithelial cell lines. The TK display assay reproducibly demonstrated known differences in HER-2/neu expression between cell lines. Several TKs, including receptor TKs Axl, Cak, fibroblast growth factor receptor 4, HEK8, HER2/neu, c-MET, RET, and nonreceptor TKs ARG, BRK, Janus kinase 1, Rak, and YES were detected in breast cancer cells. Several kinases were differentially expressed among the cell lines. Similar TK profiles were found using RNA from human breast tumors. We conclude that there is significant variability in the TK expression pattern of breast cancers. This variability should be considered when selecting TK inhibitors to treat patients.