Variant estrogen receptors and their role in liver disease.
The liver presents estrogen receptors alpha and beta. As for breast cancer, a variant form of estrogen receptor alpha transcript (ER) has been described in hepatocellular carcinoma (HCC). It is derived by an exon 5-deleted transcript (vER), which lacks the hormone-binding domain of the receptor but, being intact in the DNA-binding domain, maintains constitutive transcriptional activity. HCCs presenting vER have an extremely aggressive clinical course and are unresponsive to the antiestrogen tamoxifen. On the other hand, megestrol, a drug able to block both the wild type and the variant form of ER, influence the clinical course of HCC presenting vER. The presence of vER is associated with elevated cancer cell proliferation rate.
Villa
Erica
E
Department of Internal Medicine, Chair of Gastroenterology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy. villa.erica@unimo.it
Colantoni
Alessandra
A
Grottola
Antonella
A
Ferretti
Ilva
I
Buttafoco
Paola
P
Bertani
Helga
H
De Maria
Nicola
N
Manenti
Federico
F
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005091:Exons; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008535:Megestrol / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D016019:Survival Analysis; D013629:Tamoxifen / Q000494:pharmacology
D020847:Estrogen Receptor Modulators; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D013629:Tamoxifen; D008535:Megestrol