A family history of prostate cancer in first-degree relatives was associated with a 1.2-fold increased risk of breast cancer (95% CI: 0.98-1.50), largely a reflection of the association with ER-PR- tumors (RR = 1.5; 95% CI: 0.8-3.0).
Full-length TSG101 or its separated regions repressed ligand-dependent transcriptional activation by nuclear receptors, including androgen receptor and estrogen receptor, which play central roles in prostate carcinoma and breast carcinoma, respectively.
Our results show that the ER gene promoter was methylated in 100% (six of six) of the prostate cancer cell lines tested and all were accompanied by loss of ER mRNA expression.
The recent discovery of the classical estrogen receptor alpha (ERalpha) in androgen-insensitive prostate cancer has shed new light on the role of estrogens in endocrine therapy failure.
Both ER-alpha and ER-beta mRNAs were detected in all of the prostate cancer tissues examined, as well as in PC3 and LNCap cells, although the levels varied among specimens.
The BRCA1 gene was previously found to inhibit the transcriptional activity of the estrogen receptor [ER-alpha] in human breast and prostate cancer cell lines.
Taken together, these data indicate that, although increased expression of the AR gene might play a key role in endocrine treatment failure, it cannot be considered as the sole actor of this unresolved dilemma, and abnormalities in ER alpha and/or ER beta expression may also modulate the growth response of prostate cancer to hormone withdrawal.
The recent discovery of the classical estrogen receptor alpha (ERalpha) in metastatic and recurrent prostatic adenocarcinoma suggests that estrogens are implicated in prostate cancer progression.
When examining the effects of two polymorphisms on prostate cancer risk, homozygosity for the ESR1 XbaI restriction site together with a longer AR was more frequent among controls (32%) than cases (18%; age- and BMI-adjusted OR, 0.39; 95% CI, 0.19-0.78).
Furthermore, the absence of ER-alpha mRNA and the presence of ER-beta mRNA expression in hormone-independent and/or untreated prostate cancer cells leads to a tentative speculation of the mechanism of the hormone refractory feature of prostate cancer.
We previously reported that expression of the breast cancer susceptibility gene BRCA1 strongly inhibits the transcriptional activity of the estrogen receptor (ER-alpha) in human breast and prostate cancer cell lines but only weakly inhibits ER-alpha activity in cervical cancer cells (S. Fan et al., Science (Wash. DC), 284: 1354-1356, 1999).
We addressed this question by stably transfecting wild type (wt) ER-alpha cDNA into an invasive estrogen receptor-negative human prostate cancer cell line ARCaP.
Given the present evidence for direct control of hTERT gene expression and telomerase activity in the prostate by the ER, we suggest that this transcriptional regulator represents a possible therapeutic target in prostate cancer.
ER-beta and ER-alpha transcripts were also studied by semiquantitative reverse transcriptase polymerase chain reaction in PC-3 and LNCaP prostate carcinoma cell lines.
In summary, this study has demonstrated androgen receptor (ARStuI) and estrogen receptor (ER325) genetic polymorphisms in prostate cancer patients and its association with disease progression and metastasis.
The number of high-risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19, and the G/A in COMT) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72-5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61-10.99; P = 0.002).
Loss of expression of estrogen receptor (ER)-beta expression during prostate carcinogenesis and prevention of estrogen-mediated oxidative damage could be exploited in future PCa prevention strategies.
Treatment of PCa cell lines (LNCaP and DU145), that express little ER-beta mRNA, with a demethylating agent increased levels of receptor expression thus corroborating our in vivo findings that methylation is involved in ER-beta silencing.
The methylation status of ESR1 in 83 prostate cancer samples from patients aged 49 to 77 years (mean age at 67.4 years) was examined using the bisulfite genomic sequencing technique.