Expression of peroxisome proliferator-activated receptor-gamma in colon cancer: correlation with histopathological parameters, cell cycle-related molecules, and patients' survival.
Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, is a key regulator of adipogenic differentiation and glucose homeostasis. PPAR-gamma ligands have recently been demonstrated to affect proliferation and differentiation in cancer cells lines. The aim of the present work was to examine PPAR-gamma expression in colon cancer cases. PPAR-gamma expression was examined immunohistochemically in 86 colon cancer cases and was correlated with clinicopathological parameters, tumor proliferative capacity, cell cycle-related molecule expression, and patient survival. Positive PPAR-gamma immunostaining was prominent in 48 of 86 cases (56%). PPAR-gamma positivity was not correlated with Dukes' stage, histological grade of differentiation, lymph node and liver metastasis, venous invasion, tumor proliferative capacity, or patient survival. A statistically significant correlation was found between PPAR-gamma and the expression of cell cycle-related molecules pRb (P < 0.016), cyclin D1 (P <0.009), p16 (P<0.032), and p21 (P<0.033), while a positive trend for cyclin E was also noted (P<0.057). The pattern, intensity, and extent of PPAR-gamma expression in positive cases were not correlated with any of the examined variables. Our findings support evidence for participation of this protein in the biological mechanisms underlying carcinogenic evolution in the colon, also suggesting the importance of specific PPAR-gamma ligands as cell cycle modulators for a future therapeutic approach in colon cancer.
Theocharis
Stamatios
S
Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75 M. Asias str., Goudi, GR11527, Athens, Greece. theocharis@ath.forthnet.gr
Giaginis
Costas
C
Parasi
Aikaterini
A
Margeli
Alexandra
A
Kakisis
John
J
Agapitos
Emmanuel
E
Kouraklis
Gregorios
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000096:biosynthesis* / Q000276:immunology; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015996:Survival Rate
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D019927:Cyclin E; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D047495:PPAR gamma; D016160:Retinoblastoma Protein; D019938:Cyclin D1