Di Leo A, Barone M, Maiorano E, Tanzi S, Piscitelli D, Marangi S, Lofano K, Ierardi E, Principi M, Francavilla A
Section of Gastroenterology, Department of Emergency and Organ Transplantation (D.E.T.O.), Bari, Italy.
Dig Liver Dis. 2008 Apr;40(4):260-6. doi: 10.1016/j.dld.2007.10.018. Epub 2008 Feb 21.
A pivotal role of oestrogen receptor-beta has been suggested in colon carcinogenesis in humans. However, few data are available on oestrogen receptor-beta in colorectal pre-cancerous lesions.
In the present study, we evaluated oestrogen receptor-beta expression and its possible correlation with proliferative activity and apoptosis in colorectal adenomas and normal colon tissue.
PATIENTS/METHODS: Adenomatous tissue from 25 patients with colonic polyps, and normal tissue from 25 controls were used. Oestrogen receptor-beta expression, colonocyte proliferation (expressed as PCNA positivity) and apoptosis were evaluated.
In adenomatous tissue, a significant reduction of oestrogen receptor-beta was observed compared to normal mucosa (10.1+/-5.5% vs. 44.2+/-13.7; p<0.03), while the expression of oestrogen receptor-alpha remained unvaried. Cell proliferative activity significantly increased in adenomatous tissue compared to normal mucosa (59.3+/-7.1 vs. 18.5+/-8.8; p<0.0001), doubling the PCNA/apoptosis ratio. An inverse correlation was found between oestrogen receptor-beta and PCNA expression in adenomas (r=-0.81), a datum confirmed by confocal microscopy evaluation.
Our data demonstrate, for the first time, a significant reduction of oestrogen receptor-beta expression already in the pre-cancerous phase of colon carcinogenesis. This suggests a role of selective oestrogen receptor-beta agonists in the prevention of colorectal cancer.
雌激素受体-β在人类结肠癌发生过程中被认为起关键作用。然而,关于结直肠癌前病变中雌激素受体-β的数据很少。
在本研究中,我们评估了雌激素受体-β在结直肠腺瘤和正常结肠组织中的表达及其与增殖活性和细胞凋亡的可能相关性。
患者/方法:使用了25例结肠息肉患者的腺瘤组织和25例对照的正常组织。评估了雌激素受体-β表达、结肠细胞增殖(以PCNA阳性表示)和细胞凋亡。
与正常黏膜相比,腺瘤组织中雌激素受体-β显著降低(10.1±5.5%对44.2±13.7;p<0.03),而雌激素受体-α的表达保持不变。与正常黏膜相比,腺瘤组织中的细胞增殖活性显著增加(59.3±7.1对18.5±8.8;p<0.0001),PCNA/凋亡率增加一倍。在腺瘤中发现雌激素受体-β与PCNA表达呈负相关(r=-0.81),共聚焦显微镜评估证实了这一数据。
我们的数据首次证明,在结肠癌发生的癌前阶段雌激素受体-β表达就显著降低。这表明选择性雌激素受体-β激动剂在预防结直肠癌中发挥作用。