Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer

Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer
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DOI:
10.1007/bf02409059
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发表时间:
1996-01-01
影响因子:
3.7
通讯作者:
Cance, WG
Cance, WG
中科院分区:
医学2区
文献类型:
--
作者:
Owens, LV;Xu, LH;Cance, WG

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背景:FAK基因编码一个125 kDa的酪氨酸激酶(p125(FAK)),参与细胞黏附、运动和非锚定生长的信号转导通路。由于甲状腺癌的侵袭和转移倾向具有很大的差异性,我们研究了FAK在各种甲状腺组织中的表达。方法:我们合成了人FAK蛋白的N端重组片段,并制备了特异性的多克隆抗血清。利用Western印迹分析,我们评估了来自27例患者的30例人甲状腺组织标本中p125(FAK)的表达水平,其中包括配对的正常和恶性标本。结果:FAK蛋白表达水平与甲状腺癌侵袭性表型直接相关。P125(FAK)在滤泡癌和伴有远处转移灶的肿瘤中表达最高。而在浸润性有限的甲状腺肿瘤组织中,如乳头状癌、滤泡性腺瘤和其他非恶性甲状腺病变中,p125(FAK)的表达水平较低。此外,p125(FAK)水平可作为反映本病生物学行为的指标。
Background: The FAK gene encodes a 125-kDa tyrosine kinase (p125(FAK)) involved in signal transduction pathways used in cell adhesion, motility, and anchorage-independent growth. Because thyroid carcinomas have a wide variability in their propensity for invasion and metastasis, we studied the expression of FAK in a variety of thyroid tissues.Methods: We synthesized a recombinant N-terminal fragment of the human FAK protein and developed a specific polyclonal antisera. Using Western blot analysis, we assessed the levels of p125(FAK) expression in 30 human thyroid tissue samples from 27 patients that included paired normal and malignant specimens. Levels of FAK protein in individual tumors were quantitated by densitometric scanning of the immunoblots, and the results were correlated with tumor histology and biologic behavior.Results: The levels of FAK expression were directly correlated with thyroid carcinomas demonstrating the most aggressive phenotypes. The highest levels of p125(FAK) were seen in follicular carcinomas and tumors associated with distant metastatic foci. In contrast, neoplastic thyroid tissues with limited invasive potential, such as papillary carcinomas, follicular adenomas, and other nonmalignant thyroid lesions, showed minimal p125(FAK) expression.Conclusions: Overexpression of FAK may be part of a mechanism for invasion and metastasis of thyroid cancer. Furthermore, the levels of p125(FAK) may serve as a marker of biologic behavior in this disease.