Possible involvement of androgen receptor alterations in hepatocarcinogenesis.
BACKGROUND
Androgen receptors (ARs) act as transcription factors. An increased AR activity could be due either to mutations or to an increased expression of the receptor. AR mutations involving the hormone binding domain could increase AR function and promote carcinogenesis, as suggested for prostate cancer.


OBJECTIVE
Herein, we evaluated qualitative (point mutations involving the hormone binding domain) and quantitative AR alterations and their possible correlation with cell proliferation and tumour grading.


METHODS
Carcinomatous and non-cancerous surrounding liver tissue was collected from 14 Caucasian patients with hepatocarcinoma. They were all affected by cirrhosis with different aetiologies.


METHODS
AR missense mutations, AR mRNA and protein levels, AR distribution in the liver, liver cell proliferation, and tumour staging were evaluated by DNA sequencing, quantitative real-time PCR, Western blot analysis, immunofluorescence, PCNA immunostaining, and conventional histological techniques, respectively.


RESULTS
AR gene regions encoding the hormone binding domain did not contain any missense mutation. AR mRNA and protein levels were increased in hepatocarcinoma compared to non-cancerous surrounding tissue. Cell proliferation was significantly increased in the tumour compared to non-cancerous surrounding tissue.


CONCLUSIONS
Mutations of the AR regions studied were not involved in hepatocarcinogenesis. Elevated AR levels in transformed cells could have a tumour promoting effect by stimulating cell growth.
Barone
M
M
Section of Gastroenterology, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Ospedale Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy. m.barone@gastro.uniba.it
Margiotta
M
M
Scavo
M P
MP
Gentile
A
A
Francioso
D
D
Papagni
S
S
Castellaneta
A
A
Mallamaci
R
R
Di Leo
A
A
Francavilla
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000727:Androgen-Binding Protein / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
D000727:Androgen-Binding Protein; D011944:Receptors, Androgen