Specific receptors for 1,25-dihydroxyvitamin D3 (1,25-DR) and human colorectal carcinogenesis.
Because it is a common prerequisite for steroid responsiveness in target tissue, we investigated the presence of specific 1,25-DR in spontaneous human colorectal adenocarcinomas (ADC) and adjacent normal-appearing mucosa (NAM) from 23 operative specimens (12 male and 11 female patients). 1,25-DR was determined in cytosol by a DCC assay technique. 1,25-DR was present in 21 of 23 NAM and in only 4 of 23 HCRA. All positive ADC were well differentiated. Receptor content expressed in femtomoles/mg of protein (mean +/- SEM) was respectively 63.9 +/- 7.6 for right colon NAM and 51.3 +/- 12.9 for left colon or rectum NAM. When we compared all NAM specimens, receptor content was 56.7 +/- 8.0 femtomoles/mg of protein. No difference in 1,25-DR NAM level was observed between right colon and left colon or rectum. In adenocarcinoma the mean content was 66.5 +/- 14 fmoles/mg of protein. Scatchard analysis showed a single class of specific high-affinity saturable 1,25-DR with a dissociation constant (Kd) of 0.97 +/- 0.57 and 1.03 +/- 0.39 chi 10(-10) M in NAM and ADC respectively. These preliminary data represent the first demonstration of 1,25-DR throughout the entire human colon and indicate that the receptivity for this hormone is often lost during malignant transformation of the human colorectal mucosa. In addition, 1,25-DR could be a marker of differentiation in ADC. These preliminary results provide evidence supporting the addition of Vitamin D to the roster of developmental cancer chemopreventative agents.
Lointier
P
P
Département d'Hépato-Gastro-Entérologie, Hotel-Dieu, Clermont-Ferrand, France.
Meggouh
F
F
Pezet
D
D
Dapoigny
M
M
Dieng
P N
PN
Saez
S
S
Chipponi
J
J
D000230:Adenocarcinoma / Q000032:analysis*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002117:Calcitriol / Q000378:metabolism*; D003106:Colon / Q000032:analysis*; D003110:Colonic Neoplasms / Q000032:analysis*; D003600:Cytosol / Q000032:analysis; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000032:analysis*; D012004:Rectal Neoplasms / Q000032:analysis*
D014408:Biomarkers, Tumor; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol