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...

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Published inAnticancer research Vol. 9; no. 6; p. 1921
Main Authors Lointier, P, Meggouh, F, Pezet, D, Dapoigny, M, Dieng, P N, Saez, S, Chipponi, J
Format Journal Article
LanguageEnglish
Published Greece 01.11.1989
Subjects
Adenocarcinoma - analysis
Adult
Aged
Biomarkers, Tumor - analysis
Calcitriol - metabolism
Colon - analysis
Colonic Neoplasms - analysis
Cytosol - analysis
Female
Humans
Intestinal Mucosa - analysis
Male
Middle Aged
Receptors, Calcitriol
Receptors, Steroid - analysis
Rectal Neoplasms - analysis
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Summary: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.
ISSN:0250-7005