Magklara A, Scorilas A, López-Otín C, Vizoso F, Ruibal A, Diamandis E P
Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5. Canada M5G 1L5.
Clin Chem. 1999 Oct;45(10):1774-80.
Human glandular kallikrein (hK2) belongs to the serine protease family of enzymes and has high sequence homology with prostate-specific antigen (PSA). The physiological role of hK2 has not as yet been determined, but there is evidence that it can regulate the proteolytic activity of PSA through processing and activating pro-PSA, an inactive precursor. Thus, it is conceivable that these two secreted proteins may coexist in biological fluids. Currently, hK2 is considered an androgen-regulated and prostate-specific protein. Recently, it has been demonstrated that hK2 is expressed in the breast cancer cell line T-47D after stimulation by steroid hormones, and we reported that hK2 can be detected in a subset of breast tumor extracts. These data suggest that hK2 may be expressed in tissues other than the prostate, such as those in which PSA has already been detected. Because hK2 is a secreted protein, it may be present in various biological fluids.
We analyzed milk samples from lactating women, amniotic fluid from pregnant women, and breast cyst fluid from patients with gross breast cystic disease, using a highly sensitive and specific immunoassay for hK2.
hK2 was present in all three biological fluids. We suggest that the female breast may produce hK2 and provide evidence that hK2 may have value as an additional marker for the discrimination between type I and type II breast cysts.
The female breast produces hK2 in addition to PSA. More studies are necessary to establish the role of this kallikrein in nondiseased breast, gross breast cystic disease, and breast cancer.
人腺激肽释放酶(hK2)属于丝氨酸蛋白酶家族,与前列腺特异性抗原(PSA)具有高度的序列同源性。hK2的生理作用尚未确定,但有证据表明它可以通过加工和激活无活性前体——前PSA来调节PSA的蛋白水解活性。因此,可以想象这两种分泌蛋白可能共存于生物体液中。目前,hK2被认为是一种雄激素调节的前列腺特异性蛋白。最近,已证明hK2在类固醇激素刺激后的乳腺癌细胞系T-47D中表达,并且我们报道在一部分乳腺肿瘤提取物中可以检测到hK2。这些数据表明hK2可能在前列腺以外的组织中表达,例如那些已经检测到PSA的组织。由于hK2是一种分泌蛋白,它可能存在于各种生物体液中。
我们使用一种针对hK2的高度灵敏且特异的免疫测定法,分析了哺乳期妇女的乳汁样本、孕妇的羊水以及患有乳腺大囊肿病患者的乳腺囊肿液。
hK2存在于所有这三种生物体液中。我们认为女性乳腺可能产生hK2,并提供证据表明hK2可能作为区分I型和II型乳腺囊肿的附加标志物具有价值。
除了PSA外,女性乳腺还产生hK2。需要更多研究来确定这种激肽释放酶在正常乳腺、乳腺大囊肿病和乳腺癌中的作用。