Evidence of 1,25-dihydroxyvitamin D3-receptors in human digestive mucosa and carcinoma tissue biopsies taken at different levels of the digestive tract, in 152 patients.
Epidemiological and experimental data suggest that dietary calcium and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) are protective against colorectal cancers, while their activity on colon mucosa still remains unknown. Since the presence of receptors is required for steroid action, specific 1,25-(OH)2D3 receptors were investigated in biopsies taken at different levels of the digestive tract from the oesophagus to the rectum and in pancreas. The total study involved biopsies from 152 patients. In 82% of the cases they were paired biopsies in adenocarcinoma tissue and in adjacent normal mucosa (NM). There were 120 operated on for colorectal adenocarcinoma (HCRA). 1,25-(OH)2D3 receptor was assayed in tissue extract by the dextran-coated charcoal (DCC) technique and also characterised by sucrose density gradient centrifugation. Scatchard analyses showed a single class of specific high affinity-low capacity sites binding for 1,25-(OH)2D3 with a Kd = 1.48 +/- 0.8 x 10(-10) M (n = 119). The sedimentation coefficient of the steroid receptor complex was approximately 3.2 S. The incidence of 1,25-(OH)2D3 receptors was significantly higher in NM (82.5%) than in HCRA (34.5%). In HCRA this incidence decreased from right colon (64.7%) to left colon (27.7%) and rectum (15%). All positive HCRA in left colon and rectum (16/76) were histologically well differentiated. The receptor content in NM and HCRA was in the same range: (median) 10-314 (58) and 13-175 (64) fmol/mg protein. These data suggest that 1,25-(OH)2D3 may modulate calcium transport in colon, as in the intestine. Also, loss of receptivity to 1,25-(OH)2D3 is observed as associated with malignant transformation of the human colorectal mucosa.
Meggouh
F
F
Service de Biologie Médicale, Centre Léon Bérard, Lyon, France.
Lointier
P
P
Pezet
D
D
Saez
S
S
D001706:Biopsy; D002117:Calcitriol / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol