Creighton Chad J
Department of Medicine, Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX 77030, USA.
BMC Genomics. 2007 Jun 28;8:199. doi: 10.1186/1471-2164-8-199.
The development of resistance to hormone therapy in both breast and prostate cancers is attributed to tens of thousands of patient deaths every year.
From analyses of global gene expression profile data, a nonrandom amount of overlap was observed between the set of genes associated with estrogen receptor negative (ER-), hormone independent breast cancer and the set of genes associated with androgen independent (AI) prostate cancer. A set of 81 genes was identified that were differentially expressed between ER- and ER+ clinical breast tumors and breast cancer cell lines and that showed concordant expression in AI versus AS (androgen sensitive) prostate cell lines. This common gene signature of hormone independence was used to identify a subset of clinically localized primary prostate tumors that shared extensive similarities in gene transcription with both ER- breast and AI prostate cell lines and that tended to show concurrent deactivation of the androgen signaling pathway. Both ER- breast and AI prostate cell lines were significantly enriched for transcriptional targets of signaling via epidermal growth factor receptor (EGFR).
This study indicates that the growth- and survival-promoting functions of hormone receptors can be bypassed in a subset of both breast and prostate cancers by the same growth factor signaling pathways, which holds implications for the use of targeted therapy regimens.
乳腺癌和前列腺癌中激素治疗耐药性的发展每年导致数万人死亡。
通过对全球基因表达谱数据的分析，在与雌激素受体阴性（ER-）、激素非依赖性乳腺癌相关的基因集和与雄激素非依赖性（AI）前列腺癌相关的基因集之间观察到非随机数量的重叠。鉴定出一组81个基因，这些基因在ER-和ER+临床乳腺肿瘤及乳腺癌细胞系之间差异表达，并且在AI与AS（雄激素敏感）前列腺细胞系中表现出一致的表达。这种激素非依赖性的共同基因特征被用于鉴定临床局限性原发性前列腺肿瘤的一个子集，该子集在基因转录方面与ER-乳腺癌和AI前列腺细胞系具有广泛的相似性，并且倾向于显示雄激素信号通路的同时失活。ER-乳腺癌和AI前列腺细胞系均显著富集表皮生长因子受体（EGFR）信号传导的转录靶点。
本研究表明，在乳腺癌和前列腺癌的一个子集中，激素受体的生长和生存促进功能可以通过相同的生长因子信号通路被绕过，这对靶向治疗方案的使用具有启示意义。
