Several studies have described increased or decreased levels of PPARγ expression in different human tumour tissue as compared to normal mucosa [19–21]. Hence, taking into consideration the diversity of human cancer, the expression of PPARγ may likely be dependent on tissue specificity and/or mutational events that are prerequisite for cancer development. In our study, real time RT-PCR analysis demonstrates a significant enhancement in the expression of PPARγ in colorectal tumours as compared to normal surrounding mucosa. Few studies have investigated the expression of PPARγ in human colorectal carcinoma in relation to normal mucosa. Previously, the comparison of PPARγ expression levels in 11 human colon adenocarcinomas revealed no change in comparison to normal mucosa . In a recent study an increase of PPARγ expression in comparison to normal mucosa it has been observed in 25% (four) of patients with colorectal tumour  These contrasting results could be attributed to differences in methodological procedures as well as to the number of patients analyzed. With regard to the role of PPARγ in colon cancer, the available data are conflicting and mostly obtained in cell lines or in animal models [24–27]. On the other hand, it is well known that polyamine metabolism is an integral component of the mechanism of colorectal carcinogenesis [9, 28]. In this study, a close and positive correlation was observed between the PPARγ and SSAT expression both in normal and neoplastic human colorectal tissues. Studies performed with colorectal tumour cell lines have shown that cells transfected with the PPARγ restored the SSAT promoter activity, and an activated PPARγ could increase SSAT expression in these cells . Thus, our findings in human tissue are compatible with the in vitro studies about the transcriptional induction of PPARγ on the SSAT gene.
In the light of these data, we suggest that, in colorectal normal mucosa, PPARγ induces SSAT expression and influences polyamine availability, regulating cell proliferation and differentiation. In fact, it is known that the requirement of polyamines in cell growth is typically met by a biosynthetic pathway regulated by ODC and balanced by a polyamine catabolic pathway regulated by SSAT .
In colorectal tumour tissue, we observed an increase in PPARγ and SSAT expression as well as in SSAT activity.
The relationship between SSAT and cancer is only now being defined. In this respect, in vitro and in vivo studies are consistent with the notion that SSAT suppresses cell growth and tumour development [30, 31]. On the contrary, a Min mouse model in which SSAT expression promotes tumorigenesis has been proposed. . Furthermore, the role of SSAT in the polyamine metabolism in the cancer tissue seems to be tissue dependent. In fact, it has been observed that the increase in SSAT activity leads to polyamine pool depletion and growth inhibition in breast tumour [12, 33].
On the other hand, in prostatic cancer the SSAT overexpression induces growth inhibition without determining polyamine pool depletion since SSAT activity seems to modulate ODC activity [11, 34].
In this study, we report both higher polyamine levels and ODC activity in neoplastic tissue samples than in normal ones, thus confirming our previous data and those of other groups obtained in human colorectal cancer or in other types of carcinoma [35–39].
We have also found that while colon cancer tissue exhibits about a 13-fold increase of the ODC activity in comparison to normal tissue, SSAT activity rises by 1.5-fold only. The tumour polyamine pool seems to be maintained at higher levels by a robust increase in ODC activity not properly balanced by a severe increase in SSAT activity. Therefore, the SSAT response could be secondary to a pro-cancerous increase in ODC activity and polyamine levels. In this direction, we can suppose that the increase in polyamine catabolic activity, as a result of PPARγ induction without a concomitant downregulation of the polyamine biosynthetic pathway, could be insufficient for counteracting tumour development.
Our findings about PPARγ and polyamine metabolism in mutated K-ras colorectal cancer seem to follow this direction. In fact, we have detected higher levels of PPARγ and SSAT expression, as well as higher SSAT activity, in mutated K-ras samples. These data suggest that in cancer tissue with high rate of proliferation and likely with enhanced polyamine levels and ODC activity , there is an attempt to restore a growth control via SSAT with a mechanism involving PPARγ. However, in a vitro study, it has been shown that mutated K-ras suppressed the SSAT expression via a transcriptional mechanism involving the PPARγ signalling pathway . The in vitro findings may not be directly relevant to the in vivo effects and different tumour models can result in diversified functional outcome.