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Peroxisome proliferator-activated receptors (PPAR) are transcription factors
belonging to the nuclear receptor family. Three isotypes of PPAR have been described in
humans (a, NUC-1 also called /3 or ù; and y). PPAR have been implicated in a variety of
biological processes including colon cancer. We have studied the expression of PPAR in
colonic tissues in three biological situations: during development of the human fetal digestive
tract, in Caco-2 cells used as a model of enterocyte-like differentiation and in biopsies from
tumoral and normal adjacent human colon.
The PPAR subtypes are expressed as early as 7 weeks of foetus development in cell
types of endoderm and mesoderm origins. The presence of PPARy protein is found by
Western blotting and that of the encoding mRNA by nuclease-81 protection assay,
confirming that this subtype is not adipocyte-specific. PPARa, PPAR~
and PPARyexhibit
different spatio-temporal patterns of expression during morphogenesis of the digestive tract.
Whatever the stage and the gut region (except the stomach) examined, PPARy is expressed
at a high level, suggesting some fundamental role for this receptor in development and/or
physiology of the human digestive tract.
The expression of PPARa and y was next studied in Caco-2 cells. This cell line
exhibits enterocyte-like differentiation during long term culture. We showed by
immunohistochemistry that both isotype protein levels increased gradually during cell
differentiation Using Nuclease 81 protection assay, we demonstrated
that there is not a
concomitant increase in the transcriptional level of PPAR subtypes, especially PPARa and
isoforme PPARY2 which seemed to be regulated at the translationallevel.
Since PPARy has been involved in human colon carcinoma, we finally investigated
the expression of this PPAR subtype in biopsies obtained from human colon
adenocarcinoma. At the transcriptional level, PPARy was less abundant in tumours than in
normal-paired tissues. In contrast, using immunohistochemistry we showed that the
PPARy protein amount was more abundant in tumoral tissues. In addition PPARy
immunostaining was exclusively found in cytoplasm. Moreover, in normal adjacent tissues
PPARy was present in the upper one-third of the crypts suggesting that PPARy expression is
associated to the differentiation/maturation process of columnar cells.
PPAR, Colorectal cancer, development, Caco-2