[Expression and clinical significance of Ser10 phosphorylated p27(kip1) protein in human breast carcinoma]

Zhonghua Yi Xue Za Zhi. 2017 May 16;97(18):1396-1399. doi: 10.3760/cma.j.issn.0376-2491.2017.18.009.
[Article in Chinese]

Abstract

Objective: To explore the expression and clinicopathological significance of Ser10 phosphorylated p27(kip1)(P-p27Ser10) protein in human breast carcinoma tissue. Methods: Tissue specimens were obtained from 111 cases with breast carcinoma from January 2004 to December 2005. And the expression of P-p27Ser10 protein for each specimen was detected by immunohistochemical (EnVision) analysis. Six representative paired samples of cancerous and paired adjacent normal tissues were collected and detected by Western blot. The relationships between the expression levels of P-p27Ser10 protein and its clinicopathological characteristics in primary breast carcinoma were retrospectively analyzed.The association of P-p27Ser10 and Jab1 protein was detected by co-immunoprecipitation method. Results: A high-level expression of P-p27Ser10 was present in cancerous tissues but not in paired adjacent normal tissues. The positive expression rate of P-p27Ser10 protein was as high as 88.3% (98/111) and 7.2% (8/111) in cancerous and paired adjacent normal tissues respectively (P<0.05). P-p27Ser10 expression was correlated with tumor size, lymph node metastasis and TNM stage (all P<0.05). P-p27Ser10 expression was significantly correlated with Ki-67 (r=0.582, P<0.05), and inversely correlated with p27 (r=-0.426, P<0.05). Co-immunoprecipitation revealed that the association of P-p27Ser10 and Jab1 protein was increased in breast carcinoma. Conclusion: Over-expression of P-p27Ser10 protein might play an important role in the pathogenesis of breast carcinoma. P-p27Ser10 protein therefore represents a novel diagnostic marker and therapeutic target in patients with breast carcinoma.

目的: 观察第10位丝氨酸磷酸化p27(kip1)(P-p27Ser10)在乳腺癌组织中的表达情况,探讨其表达的临床病理意义。 方法: 回顾性收集嘉兴市第一医院2004年1月至2005年12月行手术切除的111例乳腺癌组织标本,采用免疫组织化学EnVision二步法检测乳腺癌及相应癌旁正常组织中P-p27Ser10的表达情况并分析其与临床病理特征的相关性;提取6例新鲜乳腺癌手术标本的总蛋白并进行定量,蛋白质印迹检测乳腺癌组织与癌旁正常组织中P-p27Ser10和p27的表达;采用免疫共沉淀方法检测乳腺癌组织中P-p27Ser10与相关蛋白Jab1的结合情况。 结果: 免疫组织化学及蛋白质印迹结果均显示,P-p27Ser10在乳腺癌组织中的表达显著高于在癌旁正常组织中的表达,本组乳腺癌组织中P-p27Ser10阳性表达率为88.3%(98/111),癌旁组织中为7.2%(8/111),两组之间差异有统计学意义(P<0.05);P-p27Ser10蛋白表达与肿瘤大小、腋淋巴结转移和TNM分期有关(均P<0.05);P-p27Ser10与增殖指标Ki-67表达呈显著正相关(r=0.582,P<0.05),与p27表达呈负相关(r=-0.426,P<0.05);免疫共沉淀结果显示,在乳腺癌组织中,P-p27Ser10与Jab1蛋白结合明显增加。 结论: p27 Ser10磷酸化参与了乳腺癌的发生发展,与乳腺癌患者的腋淋巴结转移和TNM分期有关。联合检测P-p27Ser10和p27可为乳腺癌的临床诊断及预后判断提供重要参考价值。.

Keywords: Breast neoplasms; Clinicopathological characteristics; Phosphorylation; Prognosis; p27(kip1).

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Lymphatic Metastasis
  • Peptide Hydrolases
  • Prognosis

Substances

  • Biomarkers, Tumor
  • CDKN1B protein, human
  • Intracellular Signaling Peptides and Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Peptide Hydrolases