Involvement of breast epithelial-stromal interactions in the regulation of protein tyrosine phosphatase-γ (PTPγ) mRNA expression by estrogenically active agents
Involvement of breast epithelial-stromal interactions in the regulation of protein tyrosine phosphatase-γ (PTPγ) mRNA expression by estrogenically active agents
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DOI：
10.1023/a:1013343718942
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发表时间：
2002-01-01
影响因子：
3.8
通讯作者：
Lin, YC
中科院分区：
文献类型：
--
作者：
Liu, SL;Kulp, SK;Lin, YC
背景蛋白酪氨酸磷酸酶γ（PTP γ）已被认为是肾癌和肺癌中的肿瘤抑制基因。我们以前的研究结果表明，雌二醇-17 β（E-2）诱导的PTP γ抑制可能在乳腺肿瘤发生中发挥作用。Zeranol（Z）是一种具有雌激素活性的非甾体生长促进剂，在原代培养的乳腺细胞和乳腺癌细胞系中诱导雌激素反应。采用RT-PCR方法检测人乳腺组织和乳腺癌患者手术标本中PTP γ mRNA的表达。免疫组织化学染色用于定位PTP γ在人乳腺组织中。乳腺上皮细胞和基质细胞分离和共培养，以确定参与细胞间相互作用的PTP γ mRNA表达的调节E-2和Z。PTP γ mRNA在乳腺癌组织中的表达低于正常乳腺组织。在培养的正常乳腺组织中，E-2和Z均抑制PTP γ mRNA水平，抑制率接近80%，但在从正常乳腺组织分离的培养上皮细胞中的作用较小。在共培养系统中，E-2和Z抑制PTP γ mRNA在上皮细胞中比在基质细胞中的程度更大。在整个乳腺组织中，PTP γ免疫定位于上皮。用E-2或Z处理减少了PTP γ染色，表明PTP γ在蛋白水平上减少。结果表明，E-2和Z调节PTP γ在人乳腺中的表达，并且上皮-基质细胞相互作用在雌激素活性剂调节PTP γ表达中是重要的。
Background. Protein tyrosine phosphatase gamma (PTP gamma) has been implicated as a tumor suppressor gene in kidney and lung cancers. Our previous results indicate that estradiol-17 beta (E-2)-induced suppression of PTP gamma may play a role in mammary tumorigenesis. Zeranol (Z), a nonsteroidal growth promoter with estrogenic activity that is used by the US meat industry, induces estrogenic responses in primary cultured breast cells and breast cancer cell lines.Methods. PTP gamma mRNA expression in human breast tissues and cells isolated from surgical specimens of mammoplasty and breast cancer patients were detected and quantified by RT-PCR. Immunohistochemical staining was used to localize PTP gamma in human breast tissues. Breast epithelial and stromal cells were isolated and co-cultured to determine the involvement of cell-cell interaction in the regulation of PTP gamma mRNA expression by E-2 and Z.Results. PTP gamma mRNA expression was lower in cancerous than in normal breast tissues. Both E-2 and Z suppressed PTP gamma mRNA levels in cultured normal breast tissues by similar to 80%, but had a lesser effect in cultured epithelial cells isolated from normal breast tissues. In the co-culture system, both E-2 and Z suppressed PTP gamma mRNA to a greater degree in epithelial cells than in stromal cells. In whole breast tissues, PTP gamma was immunolocalized to the epithelium. Treatment with E-2 or Z diminished PTP gamma staining indicating reductions in PTP gamma at the protein level.Conclusions. The results indicate that both E-2 and Z regulate PTP gamma expression in human breast and that epithelial-stromal cells interaction is important in the regulation of PTP gamma expression by estrogenically active agents.