cell type specificity ? - (Nov/07/2005 )

glimpsed thru the posts but didn't find the answers -

i noticed the following during my siRNA assay -
(a) same siRNA works differently in different cell lines. transfection efficiency ruled out (b/c HEK gives
a worse result than Hela - using lipofectamine 2000); cell line species ruled out. results verified by
western blotting. no northern run.
( different siRNAs against the same target behave differently in different cell lines - e.g. siRNA #1 works
better in HEK than siRNA #2, but siRNA#2 works better than siRNA#1 in Hela.
results have been repeated twice - so i supposed they are probably real.

any explanations ??? great many thanks

Certainly there is a cell-type specificity issue not related to transfection efficiency because siRNA #1 works in cell A but not in cell B, but siRNA #2 works in cell B but not in A. I have observed such phenomenon for many genes. I guess such specificity may have something to do with ways how the target gene is regulated in individual cells. For example, in cell A, when the gene's mRNA is degraded by the siRNA, the cell may transcribe more mRNA to compensate the loss, while cell B may not. This is a wild guess.