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首页> 外文学位 >Co-expression of human kallikreins 2 and 3 in prostate and breast cancer: Clinical utility and mechanisms of steroid hormonal regulation.
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Co-expression of human kallikreins 2 and 3 in prostate and breast cancer: Clinical utility and mechanisms of steroid hormonal regulation.

机译：人激肽释放酶2和3在前列腺癌和乳腺癌中的共表达：类固醇激素调节的临床用途和机制。

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摘要

KLK2, encoding for human glandular kallikrein (hK2), and KLK3, encoding for prostate specific antigen (PSA/hK3), are members of the human kallikrein gene family, a subgroup of serine proteases, located on chromosome 19q13.4. The two kallikreins share striking similarities regarding structure, tissue localisation, regulation, as well as a close physiological relationship, since hK2 has been shown to cleave and activate proPSA in vitro. Elevated serum PSA level is a valuable clinical marker for management and monitoring of prostate cancer. However, it cannot always distinguish efficiently between benign and malignant prostatic disease. We examined the potential clinical utility of hK2 in the discrimination between benign prostatic hyperplasia and prostate cancer, in patients with moderately elevated PSA levels. Our results showed that the hK2/free PSA ratio could enhance significantly the value of the free/total PSA ratio, which is currently used for the discrimination between the two diseases. We also showed that PSA and hK2 levels correlate and are higher in benign than in malignant prostatic tissue, indicating that the two kallikreins are regulated by similar mechanisms. PSA has also been detected in the female breast tissue, both healthy and cancerous. We hypothesised that hK2 was also present in female breast secretions and this was verified by its detection in milk from lactating women, nipple aspirate and breast cyst fluid. Previous studies had shown that KLK3 is under steroid hormonal regulation in breast cancer cell lines. We found that KLK2 and KLK3 were differentially expressed in breast cancer in vitro after androgen stimulation. We investigated possible mechanisms that might account for those differences and we concluded that PSA and hK2 production is dependent upon an intact androgen receptor pathway, which requires the presence of specific transcriptional cofactors. This finding suggests that breast tumour screening on the level of co-factors may offer valuable insight into the complexity of signalling by androgens in breast cancer.
机译：编码人腺激肽释放酶（hK2）的 KLK2 和编码前列腺特异性抗原（PSA / hK3）的 KLK3 是人类激肽释放酶基因家族（一个亚组）的成员位于染色体19q13.4上的丝氨酸蛋白酶。两种激肽释放酶在结构，组织定位，调节以及密切的生理关系方面都具有惊人的相似性，因为已证明hK2在体外可以裂解并激活proPSA。血清PSA水平升高是管理和监测前列腺癌的重要临床标志。然而，它不能总是有效地区分良性和恶性前列腺疾病。我们检查了PSA水平适度升高的患者在区分良性前列腺增生和前列腺癌中hK2的潜在临床效用。我们的结果表明，hK2 /游离PSA比值可以显着提高游离PSA /总PSA比值，该值目前可用于区分两种疾病。我们还显示，PSA和hK2水平相关，并且在良性上高于恶性前列腺组织，这表明这两种激肽释放酶是由相似的机制调节的。在女性乳房组织中也检测到了PSA，既健康又癌变。我们假设女性乳房分泌物中也存在hK2，并且通过在哺乳期妇女的乳汁，乳头抽吸液和乳腺囊肿液中检测到hK2进行了验证。先前的研究表明， KLK3 在乳腺癌细胞系中受类固醇激素调节。我们发现 KLK2 和 KLK3 在雄激素刺激后在体外 乳腺癌中表达差异。我们调查了可能解释这些差异的可能机制，并得出结论，PSA和hK2的产生取决于完整的雄激素受体途径，这需要存在特定的转录辅因子。这一发现表明，在辅助因子水平上进行乳腺肿瘤筛查可能为了解雄激素在乳腺癌中传递信号的复杂性提供有价值的见解。

著录项

  • 作者

    Magklara, Angeliki.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Biology Molecular.; Health Sciences Oncology.
  • 学位 Ph.D.
  • 年度 2003
  • 页码 185 p.
  • 总页数 185
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;肿瘤学;
  • 关键词

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