Pankov R, Simcha I, Zöller M, Oshima R G, Ben-Ze'ev A
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
J Cell Sci. 1997 Apr;110 ( Pt 8):965-74. doi: 10.1242/jcs.110.8.965.
The co-expression of vimentin and keratin-type intermediate filaments in the same cell was often reported to correlate with increased invasiveness and a more aggressive tumorigenic phenotype. To address the possible physiological relevance of these observations, we transfected simple keratins (K8 and 18) either individually, or in combination, into a tumorigenic but non-metastatic pancreatic adenocarcinoma that expresses vimentin but no keratins. Expression of K8 resulted in the stabilization of endogenous K19 in these cells, and formation of keratin filaments containing K8 and K19. Transfection of K18 yielded unstable K18 protein, but K18 could be stabilized when K8 was co-expressed in the same cells. Clones expressing K18 alone, or together with K8, displayed a reduced ability to grow in soft agar and decreased motility when compared to control, or K8/19 expressing cells. Moreover, K18 expressing cells were dramatically inhibited in their ability to form tumors when injected into syngeneic animals. The extent of suppression in the tumorigenicity of these cells correlated with the level of K18 expressed by these cells. The results show that K18 expression in cells may result in the suppression of the motile and tumorigenic abilities of this adenocarcinoma.
波形蛋白和角蛋白型中间丝在同一细胞中的共表达常被报道与侵袭性增加和更具侵袭性的肿瘤发生表型相关。为了探究这些观察结果可能的生理相关性，我们将简单角蛋白（K8和K18）单独或联合转染到一种具有肿瘤发生能力但不转移的胰腺腺癌中，该腺癌表达波形蛋白但不表达角蛋白。K8的表达导致这些细胞中内源性K19的稳定，并形成包含K8和K19的角蛋白丝。转染K18产生不稳定的K18蛋白，但当K8在同一细胞中共表达时，K18可以稳定。与对照细胞或表达K8/19的细胞相比，单独表达K18或与K8一起表达的克隆在软琼脂中生长的能力降低，运动性下降。此外，将表达K18的细胞注射到同基因动物中时，其形成肿瘤的能力受到显著抑制。这些细胞致瘤性的抑制程度与这些细胞表达的K18水平相关。结果表明，细胞中K18的表达可能导致这种腺癌的运动和致瘤能力受到抑制。
