Enerbäck Charlotta, Porter Dale A, Seth Pankaj, Sgroi Dennis, Gaudet Justine, Weremowicz Stanislawa, Morton Cynthia C, Schnitt Stuart, Pitts Robert L, Stampl Jason, Barnhart Kerry, Polyak Kornelia
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Cancer Res. 2002 Jan 1;62(1):43-7.
We determined, by serial analysis of gene expression (SAGE) analysis of normal and DCIS (ductal carcinoma in situ) mammary epithelial cells, that psoriasin and several other genes implicated in psoriasis are aberrantly expressed in high-grade, comedo DCIS. Real-time PCR, mRNA in situ hybridization, and immunohistochemical analysis of breast carcinomas confirmed that psoriasin is frequently overexpressed in estrogen receptor-negative tumors. To gain insight into regulatory pathways that control psoriasin expression, we developed polyclonal and monoclonal antibodies and investigated mechanisms that may account for elevated levels of psoriasin in DCIS. Here, we report that loss of attachment to extracellular matrix, growth factor deprivation, and confluent conditions dramatically up-regulate psoriasin expression in MCF10A mammary epithelial cells. All of these conditions are characteristic of high-grade DCIS and psoriatic skin lesions; therefore, the same mechanisms may be responsible for increased expression of psoriasin in vitro and in vivo.
通过对正常和导管原位癌（DCIS）乳腺上皮细胞进行基因表达系列分析（SAGE），我们发现，在高级别粉刺型DCIS中，银屑素和其他一些与银屑病相关的基因存在异常表达。对乳腺癌进行的实时PCR、mRNA原位杂交和免疫组化分析证实，银屑素在雌激素受体阴性肿瘤中经常过度表达。为深入了解控制银屑素表达的调控途径，我们制备了多克隆和单克隆抗体，并研究了可能导致DCIS中银屑素水平升高的机制。在此，我们报告，与细胞外基质脱离附着、生长因子剥夺和汇合状态会显著上调MCF10A乳腺上皮细胞中银屑素的表达。所有这些情况都是高级别DCIS和银屑病皮肤病变的特征；因此，相同的机制可能导致体外和体内银屑素表达增加。
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