García Normand, Salamanca Fabio, Astudillo-de la Vega Horacio, Curiel-Quesada Everardo, Alvarado Isabel, Peñaloza Rosenda, Arenas Diego
Molecular Genetics Laboratory, Pediatric Hospital, National Medical Center Century XXI, Mexican Social Security Institute, Mexico City, Mexico.
BMC Cancer. 2005 Aug 1;5:93. doi: 10.1186/1471-2407-5-93.
Breast cancer is one of the most frequent causes of death in Mexican women over 35 years of age. At molecular level, changes in many genetic networks have been reported as associated with this neoplasia. To analyze these changes, we determined gene expression profiles of tumors from Mexican women with breast cancer at different stages and compared these with those of normal breast tissue samples.
32P-radiolabeled cDNA was synthesized by reverse transcription of mRNA from fresh sporadic breast tumor biopsies, as well as normal breast tissue. cDNA probes were hybridized to microarrays and expression levels registered using a phosphorimager. Expression levels of some genes were validated by real time RT-PCR and immunohistochemical assays.
We identified two subgroups of tumors according to their expression profiles, probably related with cancer progression. Ten genes, unexpressed in normal tissue, were turned on in some tumors. We found consistent high expression of Bik gene in 14/15 tumors with predominant cytoplasmic distribution.
Recently, the product of the Bik gene has been associated with tumoral reversion in different neoplasic cell lines, and was proposed as therapy to induce apoptosis in cancers, including breast tumors. Even though a relationship among genes, for example those from a particular pathway, can be observed through microarrays, this relationship might not be sufficient to assign a definitive role to Bik in development and progression of the neoplasia. The findings herein reported deserve further investigation.
乳腺癌是墨西哥35岁以上女性最常见的死亡原因之一。在分子水平上，许多基因网络的变化已被报道与这种肿瘤形成有关。为了分析这些变化，我们测定了不同阶段的墨西哥乳腺癌女性肿瘤的基因表达谱，并将其与正常乳腺组织样本的基因表达谱进行比较。
通过对新鲜散发型乳腺肿瘤活检组织以及正常乳腺组织的mRNA进行逆转录合成32P放射性标记的cDNA。将cDNA探针与微阵列杂交，并使用磷光成像仪记录表达水平。一些基因的表达水平通过实时RT-PCR和免疫组织化学分析进行验证。
根据表达谱，我们鉴定出两个肿瘤亚组，可能与癌症进展有关。在正常组织中未表达的10个基因在一些肿瘤中被激活。我们发现14/15个肿瘤中Bik基因持续高表达，且主要分布在细胞质中。
最近，Bik基因的产物已被证明与不同肿瘤细胞系中的肿瘤逆转有关，并被提议作为诱导包括乳腺肿瘤在内的癌症细胞凋亡的治疗方法。尽管通过微阵列可以观察到基因之间的关系，例如特定途径中的基因关系，但这种关系可能不足以确定Bik在肿瘤发生和发展中的明确作用。本文报道的研究结果值得进一步研究。
