PMID- 25961250
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150513
LR  - 20150512
IS  - 1868-1883 (Print)
IS  - 1868-1883 (Linking)
VI  - 5
IP  - 3
DP  - 2011 Mar 1
TI  - Estrogen signalling through amphiregulin may be implicated in human 
      hepatocellular carcinoma.
PG  - 153-60
LID - /j/hmbci.2011.5.issue-3/hmbci.2011.003/hmbci.2011.003.xml [pii]
LID - 10.1515/HMBCI.2011.003 [doi]
AB  - BACKGROUND: We investigated aromatase (Aro)-driven estrogen formation in 
      non-tumoral and malignant liver tissues and cells, also in relation to expression 
      of the estrogen receptors alpha and beta (ERalpha and ERbeta) and amphiregulin (AREG), aiming 
      to gain insights into the potential role of estrogens in human hepatocellular 
      carcinoma (HCC). MATERIALS AND METHODS: Chromatographic and reverse transcriptase 
      polymerase chain reaction (RT-PCR) analyses were used to assess activity and 
      expression of the Aro enzyme and AREG as well as the expression of wild-type and 
      variant ERs, both in vivo and in vitro. RESULTS: Following 24 h and 72 h 
      incubation of liver tissues or cells with testosterone, human HCC tissues and 
      HepG2 hepatoma cells showed elevated Aro activity (estrogen formation, 
      respectively, of 20% and 52%-99%). By contrast, no Aro activity could be detected 
      in non-tumoral tissues and HA22T liver cancer cells. Cirrhotic samples and Huh7 
      cells exhibited intermediate enzyme activity, with estrogen formation of 4% and 
      34%, respectively. Markedly lower or undetectable Aro mRNA levels were observed 
      in HA22T cells and non-tumoral liver tissues compared with HepG2 cells and HCC 
      samples. Cirrhotic specimens displayed variable transcript levels. Interestingly, 
      no or low expression of wild-type ERalpha and ERbeta could be observed in liver cancer 
      cells and malignant tissues. However, ubiquitous expression of the hERalpha46 variant 
      and occasional expression of the hERbeta2/Cx variant were observed in cancer tissues 
      and cells. CONCLUSIONS: It is noteworthy that the pattern of wild-type ERalpha was 
      inversely related to Aro, whilst AREG expression was consistently associated with 
      that of Aro. This combined evidence suggests that locally elevated Aro activity 
      may increase malignant cell proliferation also through AREG signalling.
FAU - Carruba, Giuseppe
AU  - Carruba G
FAU - Miceli, Vitale
AU  - Miceli V
FAU - Cocciadiferro, Letizia
AU  - Cocciadiferro L
FAU - Zarcone, Maurizio
AU  - Zarcone M
FAU - Agostara, Biagio
AU  - Agostara B
FAU - Montalto, Giuseppe
AU  - Montalto G
FAU - Granata, Orazia M
AU  - Granata OM
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Horm Mol Biol Clin Investig
JT  - Hormone molecular biology and clinical investigation
JID - 101538885
EDAT- 2011/03/01 00:00
MHDA- 2011/03/01 00:01
CRDT- 2015/05/12 06:00
PHST- 2010/12/23 00:00 [received]
PHST- 2011/01/12 00:00 [accepted]
PHST- 2015/05/12 06:00 [entrez]
PHST- 2011/03/01 00:00 [pubmed]
PHST- 2011/03/01 00:01 [medline]
AID - /j/hmbci.2011.5.issue-3/hmbci.2011.003/hmbci.2011.003.xml [pii]
AID - 10.1515/HMBCI.2011.003 [doi]
PST - ppublish
SO  - Horm Mol Biol Clin Investig. 2011 Mar 1;5(3):153-60. doi: 10.1515/HMBCI.2011.003.