Shaw Julie L V, Diamandis Eleftherios P
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Clin Chem. 2007 Aug;53(8):1423-32. doi: 10.1373/clinchem.2007.088104. Epub 2007 Jun 15.
Kallikreins (KLKs) are a group of 15 secreted serine proteases. Some KLKs are established or candidate cancer biomarkers, but for most the physiological function is unknown. We characterized the protein and mRNA abundance patterns of all 15 KLKs in multiple panels of human tissues and biological fluids.
We used sensitive and specific sandwich-type ELISAs for each KLK. Reverse transcription PCR was used for transcript amplification. Multiple panels of human tissue extracts (adult and fetal) were tested, along with various biological fluids.
Quantitative protein expression data on 7 sets of adult and 3 sets of fetal tissues were collected for all 15 KLKs. KLKs were also quantified in the following biological fluids: seminal plasma, breast milk, follicular fluid, breast cyst fluid, breast cancer cytosol, amniotic fluid, ovarian cancer ascites, cerebrospinal fluid, cervicovaginal fluid, and urine. The data were used to generate heat maps of KLK concentrations in tissues and fluids and categorize KLK abundance as highly restricted (KLK2 and KLK3 in prostate), restricted (KLK5 in skin, salivary gland, breast, and esophagus; KLK6 in brain and central nervous system; KLK7 in esophagus, heart, liver, and skin; KLK8 in breast, esophagus, skin, and tonsil; KLK13 in esophagus and tonsil), or wide (KLKs 1, 4, 9, 10, 11, 12, 14, and 15).
Quantitative KLK concentrations in tissues and fluids aid in the elucidation of KLK function, and coexpression patterns provide clues for KLK participation in proteolytic cascades.
激肽释放酶(KLKs)是一组15种分泌型丝氨酸蛋白酶。一些KLKs是已确定的或候选的癌症生物标志物,但大多数KLKs的生理功能尚不清楚。我们对多组人类组织和生物体液中所有15种KLKs的蛋白质和mRNA丰度模式进行了表征。
我们对每种KLK使用了灵敏且特异的夹心型酶联免疫吸附测定法(ELISA)。逆转录聚合酶链反应(RT-PCR)用于转录本扩增。对多组人类组织提取物(成人和胎儿)以及各种生物体液进行了检测。
收集了所有15种KLKs在7组成人组织和3组胎儿组织中的定量蛋白质表达数据。还对以下生物体液中的KLKs进行了定量:精浆、母乳、卵泡液、乳腺囊肿液、乳腺癌细胞溶质、羊水、卵巢癌腹水、脑脊液、宫颈阴道液和尿液。这些数据用于生成组织和体液中KLK浓度的热图,并将KLK丰度分类为高度受限(前列腺中的KLK2和KLK3)、受限(皮肤、唾液腺、乳腺和食管中的KLK5;脑和中枢神经系统中的KLK6;食管、心脏、肝脏和皮肤中的KLK7;乳腺、食管、皮肤和扁桃体中的KLK8;食管和扁桃体中的KLK13)或广泛(KLK1、4、9、10、11、12、14和15)。
组织和体液中的KLK定量浓度有助于阐明KLK的功能,共表达模式为KLK参与蛋白水解级联反应提供了线索。