Shapiro Ellen, Huang Hongying, Ruoff Rachel, Lee Peng, Tanese Naoko, Logan Susan K
Department of Urology, New York University School of Medicine, New York, New York, USA.
J Urol. 2008 Jun;179(6):2435-9. doi: 10.1016/j.juro.2008.01.091. Epub 2008 Apr 23.
The HP1 family of evolutionarily conserved proteins regulates heterochromatin packaging, in addition to a less defined role in the regulation of euchromatic genes. To examine the possible role of HP1 proteins in fetal prostate development and prostate cancer the protein expression of HP1alpha, beta and gamma was evaluated in human archival tissue.
Tissue sections from human prostate cancer and fetal prostate were examined using antibodies against HP1 isoforms to evaluate HP1 modulation in cancer and development. Western blot analysis of HP1 proteins was also performed in extracts of cultured prostate cancer cells.
HP1alpha, beta and gamma are differentially regulated in various cellular compartments in prostate development. HP1alpha is not expressed at 14 or 24 weeks of prostate development but it is expressed in adult prostate tissue. HP1beta is highly expressed at 14 and 24 weeks, and it appears predominantly in epithelial cells compared to HP1gamma, which is expressed at equal levels in epithelial and stromal cells. All 3 HP1 isoforms show altered expression in prostate cancer compared to that in normal adult prostate tissue.
HP1 proteins are tightly regulated during prostate development. In the adult prostate HP1alpha, beta and gamma antibodies detect high levels of HP1 antigen in a contiguous layer of epithelial cells. However, the detection of HP1 in prostate cancer ranges from undetectable to inconsistent staining of noncontiguous epithelial cells.
进化上保守的HP1蛋白家族除了在常染色质基因调控中作用尚不明确外，还调控异染色质包装。为了研究HP1蛋白在胎儿前列腺发育和前列腺癌中的可能作用，我们在人类存档组织中评估了HP1α、β和γ的蛋白表达。
使用针对HP1亚型的抗体检查人类前列腺癌和胎儿前列腺的组织切片，以评估癌症和发育过程中HP1的调节情况。还对培养的前列腺癌细胞提取物进行了HP1蛋白的蛋白质印迹分析。
在前列腺发育的各个细胞区室中，HP1α、β和γ受到不同的调节。在前列腺发育的14周或24周时，HP1α不表达，但在成人前列腺组织中表达。HP1β在14周和24周时高度表达，与HP1γ相比，它主要出现在上皮细胞中，HP1γ在上皮细胞和基质细胞中的表达水平相同。与正常成人前列腺组织相比，所有3种HP1亚型在前列腺癌中的表达均发生改变。
在前列腺发育过程中，HP1蛋白受到严格调控。在成人前列腺中，HP1α、β和γ抗体在相邻的一层上皮细胞中检测到高水平的HP1抗原。然而，在前列腺癌中检测到的HP1水平从无法检测到到非相邻上皮细胞的不一致染色不等。
