Differential Regulation of TauT by Calcitriol and Retinoic Acid via VDR/RXR in LLC-PK1 and MCF-7 Cells - Advances in Experimental Medicine and Biology - page 279

Fig. 27.2 ( continued )

Deletion of regulatory region of the TauT promoter, which contains several tran-
scription factors (including two AP1 sites), abolished the effect of RA/1,25(OH) 2 D 3
on TauT expression. These findings suggest that the synergetic regulation of TauT
expression by 1,25(OH) 2 D 3 and RA may require the formation of the RXR/VDR
complex, which in turn binds to the TauT promoter region to regulate TauT expres-
sion. Activation of RXR by RA appears to be critical for upregulation of TauT in
LLC-PK1 cells.

27.3.3 Regulation of TauT Expression by 1,25(OH) 2 D 3 and RA

in MCF-7 Cells

To study whether 1,25(OH) 2 D 3 and/or RA plays a role in TauT regulation in MCF-7
cells, the approaches used were similar to those described for the LLC-PK1 cells
experiments. As shown in Fig. 27.3 , 1,25(OH) 2 D 3 or atRA alone showed only a slight
effect on the expression of TauT . However, a combination of 1,25(OH) 2 D 3 and atRA
significantly decreased expression of TauT (as determined by reporter gene assay;
Fig. 27.3a ), taurine uptake (Fig. 27.3b ), and Western blot analysis (Fig. 27.3c, d ).
Interestingly, 9-cis RA showed little effect on TauT expression with or without
1,25(OH) 2 D 3 in MCF-7 cells (Fig. 27.3f ), suggesting that regulation of TauT by 9- cis
RA or atRA occurs via different mechanisms in MCF-7 cells compared to LLC-PK1
cells. A summary of regulation of the TauT gene by 1,25(OH) 2 D 3 and RA in LLC-PK1
and MCF-7 cells is shown in Table 27.1 and further depicted in Fig. 27.4 .