Nuclear localization of KLF4 is associated with an aggressive phenotype in early-stage breast cancer
Nuclear localization of KLF4 is associated with an aggressive phenotype in early-stage breast cancer
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DOI：
10.1158/1078-0432.ccr-03-0484
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发表时间：
2004-04-15
影响因子：
11.5
通讯作者：
Ruppert, JM
中科院分区：
文献类型：
--
作者：
Pandya, AY;Talley, LI;Ruppert, JM
目的：Kruppel样转录因子KLF 4/ GKLF在体外诱导恶性转化和缓慢生长表型。虽然KLF 4的表达增加，在大多数情况下的乳腺癌，这是未知的，这些情况下是否代表一个不同的亚型与不同的临床outcome.Experimental设计：我们研究了KLF 4的表达免疫染色146例人原发性浸润性导管癌的乳腺。染色模式与临床结果和既定的预后factors.Results：亚细胞定位表现出个案到个案的变化。具有高核染色和低胞质染色的肿瘤被称为1型。对于患有早期疾病的患者（即，I期或IIA期），I型染色与乳腺癌的最终死亡相关（风险比，2.8; 95%置信区间，1.23-6.58; P = 0.011）。这种关联在早期癌症和小原发性肿瘤患者中更强（即，直径小于或等于2.0 cm;危险比为4.3; 95%可信区间为1.75-10.62; P < 0.001）。对于早期疾病患者，多变量分析表明，I型染色与预后独立相关（调整后的风险比为2.6; 95%置信区间为1.10-6.05; P = 0.029）。I型染色还与高组织学分级（P = 0.032）、Ki 67表达增加（P = 0.016）和BCL 2表达减少（P = 0.032）相关。在体外，KLF 4被定位在转化的RK 3E上皮细胞的细胞核内，与此转录因子在诱导恶性transformation.Conclusions的核功能一致：结果表明，KLF 4在乳腺癌细胞的细胞核中的定位是一个预后因素，并确定KLF 4作为早期浸润性导管癌的侵袭性表型的标志物。
Purpose: The Kruppel-like transcription factor KLF4/ GKLF induces both malignant transformation and a slow-growth phenotype in vitro. Although KLF4 expression is increased in most cases of breast cancer, it was unknown whether these cases represent a distinct subtype with a different clinical outcome.Experimental Design: We examined expression of KLF4 by immunostaining 146 cases of human primary infiltrating ductal carcinoma of the breast. Staining patterns were correlated with clinical outcome and with established prognostic factors.Results: Subcellular localization exhibited case-to-case variation. Tumors with high nuclear staining and low cytoplasmic staining were termed type 1. For patients with early-stage disease (i.e., stage I or IIA), type I staining was associated with eventual death because of breast cancer (hazard ratio, 2.8; 95% confidence interval, 1.23-6.58; P = 0.011). The association was stronger in patients with early-stage cancer and small primary tumors (i.e., less than or equal to2.0 cm in diameter; hazard ratio, 4.3; 95% confidence interval, 1.75-10.62; P < 0.001). For patients with early-stage disease, multivariate analysis indicated that type I staining was independently associated with outcome (adjusted hazard ratio 2.6; 95% confidence interval, 1.10-6.05; P = 0.029). Type I staining was also associated with high histological grade (P = 0.032), increased expression of Ki67 (P = 0.016), and reduced expression of BCL2 (P = 0.032). In vitro, KLF4 was localized within the nucleus of transformed RK3E epithelial cells, consistent with a nuclear function of this transcription factor during induction of malignant transformation.Conclusions: The results suggest that localization of KLF4 in the nucleus of breast cancer cells is a prognostic factor and identify KLF4 as a marker of an aggressive phenotype in early-stage infiltrating ductal carcinoma.