Receptors for and bioresponses to 1,25-dihydroxyvitamin D in a human colon carcinoma cell line (HT-29).
Human colon carcinoma (HT-29) cells were examined for their capacity to bind and respond to 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]. These cells are known to differentiate and increase their population doubling time when galactose is substituted for glucose in their media. High-affinity and specific binding of 1,25-(OH)2[3H]D3 was observed in extracts of these cells grown in glucose. The binder sedimented in sucrose gradients and eluted from DEAE-cellulose columns in a manner indistinguishable from rabbit intestinal 1,25-(OH)2D3-receptor. Smaller amounts of this binder were seen in HT-29 cells grown in galactose. Both glucose-fed and galactose-fed cells exhibited a dose-dependent decrease in growth rate on exposure to 10(-12) to 10(-6) mol/L 1,25-(OH)2D3. Ultrastructural examination of galactose-fed and glucose + 1,25-(OH)2D3-treated cells showed enterocytic differentiation and features that were not distinguishable between these groups. Sucrase activity was higher in galactose-fed cells and did not change with 1,25-(OH)2D3 treatment. However, the lower sucrase activity in glucose-fed cells increased after exposure to 10(-8) mol/L 1,25-(OH)2D3. These results indicate receptor content and bioresponsivity to 1,25-(OH)2D3 in a human enterocytic cell line, suggesting that it will be a useful model for the study of the mechanisms of action of this sterol.
Harper
K D
KD
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Iozzo
R V
RV
Haddad
J G
JG
D002117:Calcitriol / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002455:Cell Division; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003470:Culture Media; D004247:DNA / Q000378:metabolism; D005690:Galactose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D013393:Sucrase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003470:Culture Media; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D004247:DNA; D013393:Sucrase; D002117:Calcitriol; D005947:Glucose; D005690:Galactose