Yamashita Hiroko, Iwase Hirotaka
Department of Surgery II, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-ku, Nagoya 467-8601, Japan.
Breast Cancer. 2002;9(4):312-8. doi: 10.1007/BF02967610.
Estrogen receptor (ER) has been a successful target for effective prevention and treatment strategies in breast cancer, whereas growth factors and their signaling molecules are proving to be effective treatment targets as well. Understanding the interaction between ER and growth factor signaling pathways should provide clues to optimal treatment approaches and new strategies to overcome and prevent endocrine resistance. Cross-talk between ER and signal transducer and activator of transcription 5 (Stat5) has also been reported. Stat5 regulates growth, differentiation, and survival of mammary and hematopoietic cells. The role of Stat5 in breast cancer has not been established, although Stat5 is critical for some hematopoietic malignancies. We have analyzed the role of Stat5 in the progression of ER-positive breast cancer cells such as T47D and MCF7 in which Stat5b is constitutively activated. Adenoviral-mediated dominant-negative Stat5 induced apoptosis in T47D cells but not in caspase-3 negative MCF7 cells. Our study indicates that targeting Stat5 may represent a new strategy to suppress estrogen receptor activity and induce apoptosis in Stat5-activated, ER-positive breast cancer.
雌激素受体（ER）一直是乳腺癌有效预防和治疗策略的成功靶点，而生长因子及其信号分子也被证明是有效的治疗靶点。了解ER与生长因子信号通路之间的相互作用，应为最佳治疗方法以及克服和预防内分泌抵抗的新策略提供线索。也有报道称ER与信号转导子和转录激活子5（Stat5）之间存在相互作用。Stat5调节乳腺和造血细胞的生长、分化及存活。尽管Stat5对某些造血系统恶性肿瘤至关重要，但其在乳腺癌中的作用尚未明确。我们分析了Stat5在ER阳性乳腺癌细胞（如T47D和MCF7，其中Stat5b持续激活）进展中的作用。腺病毒介导的显性负性Stat5可诱导T47D细胞凋亡，但不能诱导caspase-3阴性的MCF7细胞凋亡。我们的研究表明，靶向Stat5可能是一种抑制雌激素受体活性并诱导Stat5激活的ER阳性乳腺癌细胞凋亡的新策略。
