Contrasting effects of K8 and K18 on stabilizing K19 expression, cell motility and tumorigenicity in the BSp73 adenocarcinoma.
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.
Pankov
R
R
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Simcha
I
I
Zöller
M
M
Oshima
R G
RG
Ben-Ze'ev
A
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D007633:Keratins / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D007633:Keratins