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 283

cells persists after siRNA knockdown, which suggests that these antiproliferative
influences do not rely on the classical vitamin D pathway per se (Costa et al. 2009 ) .
In our present study, stimulation of MCF-7 cells with all- trans RA and 1,25(OH) 2 D 3
was antiproliferative and induced apoptosis in association with reduced TauT
expression. Whether these 1,25(OH) 2 D 3 -induced changes in MCF-7 cells occur, at
least in part, by their influence on TauT is certainly a topic for greater study.
Based upon these findings, we speculate that the differences in regulation of the
TauT gene and its transporter protein in breast tissue relate to the role of the breast
in providing nutrients to the suckling infant. Taurine should be retained in breast
milk to benefit the suckled mammal who requires the amino acid for central nervous
system and retinal development and because of its role in the conjugation of bile
acids in the infant gut (Sturman et al. 1991 ). In carnivores such as bears and felids
that conjugate their bile acids only with taurine and not with glycine, there is a
nutritional requirement for higher milk concentrations of taurine. This has been
shown in the analysis of taurine in milk samples from polar bears (Hedberg et al.
2011 ) as well as other animals. Vitamins A and D and their metabolites could poten-
tially influence expression of the apical taurine transporter and downregulate the
TauT gene and its transporter protein. This, in turn, could lead to greater retention
of taurine in the milk to be available for the suckling mammal.
Does vitamin D status in lactating human mothers influence the concentration of
taurine in breast milk? There is no clear answer yet because in series measuring human
milk taurine concentrations, vitamin D status was not assessed. Human milk taurine
values depend upon the stage of lactation and mother's diet, but range from 150 to
683 mmol/l with an approximate mean of 350 mmol/l (Kim et al. 1998 ; Pasantes-
Morales et al. 1995 ; Rassin et al. 1978 ; Shubat et al. 1989 ; Stapleton et al. 1997 ) . The
taurine content of breast milk of Mexican women from urban and rural areas has been
compared (Pasantes-Morales et al. 1995 ). Taurine content in milk from urban women
was 332-357 mmol/l, essentially the same as in American and Canadian women. Milk
taurine content was significantly lower in the rural group (23-259 mmol/l). Vitamin D
deficiency is more common in Mexican populations living in Mexico (Elizondo-
Montemayor et al. 2010 ; Mithal et al. 2009 ; Romieu and Lajous 2009 ) and the USA
(Looker et al. 2011 ). These results suggest that a prospective survey of milk taurine
content and serum 25(OH)D 3 values may be of interest.

27.5 Conclusion

The taurine transporter is differentially regulated by 1,25(OH) 2 D 3 and retinoic acid
in a cell type- and tissue type-dependent manner. In LLC-PK1 renal proximal tubule
cells, TauT is upregulated, whereas in MCF-7 human breast cancer cells, there is
downregulation after 1,25(OH) 2 D 3 or RA exposure. This regulation of TauT by
1,25(OH) 2 D 3 and by retinoic acid requires the activation of both vitamin D receptors
(VDR) and retinoic acid receptors (RXR) and formation of a VDR/RXR complex.
It appears that regulation of TauT by 1,25(OH) 2 D 3 and RA occurs at the transcriptional