Yousef G M, Chang A, Diamandis E P
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
J Biol Chem. 2000 Apr 21;275(16):11891-8. doi: 10.1074/jbc.275.16.11891.
Kallikreins are a subgroup of serine proteases and these proteolytic enzymes have diverse physiological functions in many tissues. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. In rodents, kallikreins constitute a large multigene family, but in humans, only three genes were identified. By using the positional candidate gene approach, we were able to identify a new kallikrein-like gene, tentatively named KLK-L4 (for kallikrein-like gene 4). This new gene maps to chromosome 19q13. 3-q13.4, is formed of five coding exons and four introns, and shows structural similarity to other kallikreins and kallikrein-like genes. KLK-L4 is expressed in a variety of tissues including prostate, salivary gland, breast, and testis. Our preliminary results show that KLK-L4 is down-regulated, at the mRNA level, in breast cancer tissues and breast cancer cell lines. Its expression is regulated by steroid hormones in the breast cancer cell line BT-474. This gene may be involved in the pathogenesis and/or progression of breast cancer and may find applicability as a novel cancer biomarker.
激肽释放酶是丝氨酸蛋白酶的一个亚群，这些蛋白水解酶在许多组织中具有多种生理功能。越来越多的证据表明，许多激肽释放酶与癌症发生有关。在啮齿动物中，激肽释放酶构成一个庞大的多基因家族，但在人类中，仅鉴定出三个基因。通过使用定位候选基因方法，我们能够鉴定出一个新的激肽释放酶样基因，暂命名为KLK-L4（激肽释放酶样基因4）。这个新基因定位于19号染色体的19q13.3-q13.4区域，由五个编码外显子和四个内含子组成，并且与其他激肽释放酶和激肽释放酶样基因具有结构相似性。KLK-L4在多种组织中表达，包括前列腺、唾液腺、乳腺和睾丸。我们的初步结果表明，在乳腺癌组织和乳腺癌细胞系中，KLK-L4在mRNA水平上表达下调。在乳腺癌细胞系BT-474中，其表达受类固醇激素调节。该基因可能参与乳腺癌的发病机制和/或进展，并且可能作为一种新型癌症生物标志物具有应用价值。
