Overexpression of vimentin: role in the invasive phenotype in an androgen-independent model of prostate cancer.
The androgen-sensitive LNCaP prostate cancer cell line is less invasive than hormone-insensitive lines. CL1, an aggressive, hormone-insensitive LNCaP subline derived by continuous passaging in hormone-depleted medium, was compared with the parental cell line by cDNA microarray analysis. The gene coding for the intermediate filament protein vimentin was found to be highly up-regulated in the CL1 subline. This difference was confirmed by Northern and Western blots and visualized by immunofluorescence microscopy. To assess the contribution of vimentin to the invasive phenotype, LNCaP cells were stably transfected to overexpress vimentin, and the CL1 cells were transfected with vimentin antisense construct. The invasiveness of the transfected cells was tested using an in vitro invasion assay. We were able to demonstrate that decreasing vimentin expression in the constitutively vimentin-expressing CL1 cells led to a significant decrease in their invasiveness but that forcing expression of vimentin in the LNCaP cells did not augment their invasiveness. These findings imply that vimentin expression contributes to the invasive phenotype but cannot confer it alone.
Hamilton Regional Cancer Centre, Ontario, L8V 5C2 Canada.
Sadmeet
S
Singh
Skanda
S
Sadacharan
Scott
S
Su
Arie
A
Belldegrun
Sujata
S
Persad
Gurmit
G
Singh
D000728:Androgens / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D000728:Androgens; D016373:DNA, Antisense; D018076:DNA, Complementary; D014746:Vimentin; D007633:Keratins