Nagai Maria Aparecida, Ros Nancy, Bessa Simone Aparecida, Mourão Neto Mário, Miracca Elisabete Cristina, Brentani Maria Mitzi
Departamento de Radiologia, Disciplina de Oncologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Int J Oncol. 2003 Nov;23(5):1425-30.
There is a large and increasing body of experimental and clinical data supporting the involvement of estrogen on the proliferation of hormone-dependent breast tumors. Estrogen acts via its receptor (ER) stimulating cellular proliferation. ER and progesterone receptor (PR), which is regulated by estrogen via ER, have been used as prognostic markers in the clinical management of breast cancer patients. The aim of the present study was the identification of tumor-associated genes differentially expressed in breast tumors regarding the presence or absence of ER and PR. Using the technique of differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR) we have isolated and cloned 127 cDNA fragments that showed differential expression in either ER+/PR+ or ER-/PR- breast tumors. Sequencing analysis of these clones revealed that 119 cDNAs had homology with known sequences in the National Center of Biotechnology Information (NCBI) and 8 were novel, showing no homology to known genes. Among these differentially expressed transcripts are metabolic enzymes, ribosomal proteins, transcription factors, hypothetical proteins, cell cycle regulators, cytoskelectum related genes, cell adhesion and motility genes. Differences in gene expression profiles are likely to explain the phenotypic differences between hormone-responsive and hormone-unresponsive breast tumors.
有大量且不断增加的实验和临床数据支持雌激素参与激素依赖性乳腺肿瘤的增殖过程。雌激素通过其受体(ER)发挥作用,刺激细胞增殖。ER和孕激素受体(PR,其由雌激素通过ER调节)已被用作乳腺癌患者临床管理中的预后标志物。本研究的目的是鉴定在有或无ER和PR的乳腺肿瘤中差异表达的肿瘤相关基因。使用差异显示逆转录聚合酶链反应(DDRT-PCR)技术,我们分离并克隆了127个cDNA片段,这些片段在ER+/PR+或ER-/PR-乳腺肿瘤中表现出差异表达。对这些克隆的测序分析表明,119个cDNA与美国国立生物技术信息中心(NCBI)的已知序列具有同源性,8个是新的,与已知基因无同源性。在这些差异表达的转录本中,有代谢酶、核糖体蛋白、转录因子、假定蛋白、细胞周期调节因子、细胞骨架相关基因、细胞黏附和运动基因。基因表达谱的差异可能解释激素反应性和激素无反应性乳腺肿瘤之间的表型差异。