Annexin A8 is up-regulated during mouse mammary gland involution and predicts poor survival in breast cancer
Annexin A8 is up-regulated during mouse mammary gland involution and predicts poor survival in breast cancer
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DOI：
10.1158/1078-0432.ccr-05-0547
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发表时间：
2005-10-01
影响因子：
11.5
通讯作者：
Gusterson, BA
中科院分区：
文献类型：
--
作者：
Stein, T;Price, KN;Gusterson, BA
目的：微阵列研究已将annexin AB RNA 表达与乳腺癌的“基底细胞样”亚型联系起来，包括 BRCA1 相关癌症，其特征是细胞角蛋白 5 (CK5) 和 CK17 表达，且预后不良。我们评估了膜联蛋白 A8 对总体预后的贡献及其在正常、良性和癌组织中的表达，并探讨了膜联蛋白 A8 在乳腺中的生理作用。 实验设计：使用微阵列和逆转录 PCR，研究了小鼠乳腺发育过程中和分离的乳腺结构中的膜联蛋白 A8 表达。对培养的人腔细胞和基底细胞进行逆转录 PCR，以及对正常和良性乳腺组织进行免疫细胞化学，用于细胞定位。在 1,631 例浸润性乳腺癌的组织芯片上评估了膜联蛋白 A8s 的预后相关性及其与 CK5 的共表达。在 14 例 BRCA1 相关乳腺癌的小队列中进一步评估了共表达。结果：膜联蛋白 A8 在小鼠乳腺退化期间和青春期导管上皮中上调。膜联蛋白 A8 在培养的基底细胞中表现出优先表达，但在体内正常人乳腺组织中表现出主要的管腔表达。增生和原位癌显示基底细胞的强烈染色。膜联蛋白 A8 表达与分级 (P < 0.0001)、CK5 (P < 0.0001) 和雌激素受体状态 (P < 0.0001) 显着相关； 85.7%的BRCA1相关乳腺肿瘤共表达Annexin A8和CK5。结论：Annexin A8参与小鼠乳腺退化。在人类中，它是一种管腔表达的蛋白质，在细胞培养物和原位增生/导管癌中具有基础表达。浸润性乳腺癌中的表达对生存有显着影响（P = 0.03），但与级别或 CK5 无关。
Purpose: Microarray studies have linked Annexin AB RNA expression to a "basal cell-like" subset of breast cancers, including BRCA1-related cancers, that are characterized by cytokeratin 5 (CK5) and CK17 expression and show poor prognosis. We assessed Annexin A8s contribution to the overall prognosis and its expression in normal, benign, and cancerous tissue and addressed Annexin A8's physiologic role in the mammary gland.Experimental Design: Using microarrays and,reverse transcription-PCR, the Annexin A8 expression was studied during mouse mammary gland development and in isolated mammary structures. Reverse transcription-PCR on cultured human luminal and basal cells, along with immunocytochemistry on normal and benign breast tissues, was used for cellular localization. Annexin A8s prognostic relevance and its coexpression with CK5 were assessed on tissue arrays of 1,631 cases of invasive breast cancer. Coexpression was further evaluated on a small cohort of 14 BRCA1-related breast cancers.Results: Annexin A8 was up-regulated during mouse mammary gland involution and in pubertal ductal epithelium. Annexin A8 showed preferred expression in cultured basal cells but predominant luminal expression in normal human breast tissue in vivo. Hyperplasias and in situ carcinomas showed a strong staining of basal cells. Annexin A8 expression was significantly associated with grade (P < 0.0001), CK5 (P < 0.0001), and estrogen receptor status (P < 0.0001); 85.7% BRCA1-related breast tumors coexpressed Annexin A8 and CK5.Conclusion: Annexin A8 is involved in mouse mammary gland involution. In humans, it is a luminally expressed protein with basal expression in cell culture and in hyperplasia/ductal carcinoma in situ. Expression in,invasive breast carcinomas has a significant effect on survival (P = 0.03) but is not independent of grade or CK5.