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Panminerva Medica 2003 December;45(4):261-6

Copyright © 2009 EDIZIONI MINERVA MEDICA

lingua: Inglese

Sex steroid receptors, secondary bile acids and colorectal cancer. A possible mechanism of interaction

Berta L., Fronticelli Baldelli C., Fazzari A., Radice E., Bargoni A., Frairia R., Gaetini A.

Department of Clinical Pathophysiology University of Turin, Turin, Italy


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Aim. The aim of the ­work was to ­study in ­colon-rec­tum can­cer muco­sae the bind­ing cha­rat­er­is­tics, as sex ster­oid recep­tors.
Methods. Specific andro­gen (AR), estro­gen (ER) and pro­ges­te­rone (PgR) recep­tors ­were meas­ured in the tis­sue sam­ples of 35 ­patients (15 ­males, 20 ­females) under­go­ing colec­to­my or colo­proc­tec­to­my for aden­o­car­cin­o­ma. The char­ac­ter­is­tics of andro­gen recep­tor (AR, DHT-R: dihydrotestosterone receptor) ­were ­also inves­ti­gat­ed ­using com­pet­i­tive activ­ity of cyproterone ace­tate, cortisol, aldosterone and ster­oid-­like sub­stanc­es ­such as deoxicholic and lithocholic ­acid, ­present in the ­milieu of the con­sid­ered ­organ. Binding ­assays and com­pe­ti­tion ­tests ­were con­duct­ed ­using a char­coal dex­tran meth­od.
Results. When ­present (50%), ER and PgR recep­tors ­showed ­very low lev­els and no dif­fer­ence was not­ed ­between can­cer­ous and the sour­round­ing ­healthy muco­sa. AR ­were ­found in all sam­ples ­from ­both neo­plas­tic and non neo­plas­tic sour­rond­ing muco­sa, ­with no sig­nif­i­cant dif­fer­ence. Androgen recep­tor how­ev­er exhib­it­ed an ­altered bind­ing activ­ity in can­cer spec­i­mens. Cyproterone ace­tate did not dis­place DHT ­from AR ­while sig­nif­i­cant dis­plac­ing activ­ity was elic­it­ed by DHT, testosterone, as ­well as by lithocholic ­acid, but not by deoxycholic ­acid.
Conclusion. In can­cer­ous ­large bow­el muco­sa, andro­gen recep­tors ­show ­altered bind­ing carac­ter­is­tics. The selec­tive bind­ing of lith­o­chol­ic ­acid to AR sup­ports the hypoth­e­sis ­that ­diet-relat­ed endo­lu­mi­nal sub­stanc­es may ­play a ­role in can­cer devel­op­ment mod­el ­where molec­u­lar alter­a­tions ­such as DNA dam­age or muta­tion is the ­1st ­event.

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