雄激素敏感的人前列腺癌细胞LNCaP可产生N端成熟型和截短型两种前列腺特异性抗原异构体。

Androgen-sensitive human prostate cancer cells, LNCaP, produce both N-terminally mature and truncated prostate-specific antigen isoforms.

作者信息

Herrala A, Kurkela R, Vihinen M, Kalkkinen N, Vihko P

机构信息

Biocenter Oulu and WHO Collaborating Centre for Research on Reproductive Health, University of Oulu, Finland.

出版信息

Eur J Biochem. 1998 Jul 15;255(2):329-35. doi: 10.1046/j.1432-1327.1998.2550329.x.

DOI:10.1046/j.1432-1327.1998.2550329.x

PMID:9716373

Abstract

To characterize prostate-specific antigen (PSA) produced by cancer cells, different isoforms of PSA secreted by the human prostate cancer cells, LNCaP, were purified. LNCaP-PSA production was induced by synthetic androgen, R1881. LNCaP-PSA was separated into four pools. The molecular mass of LNCaP-PSA isoforms in these pools was 34 kDa under reducing conditions and 29 kDa under nonreducing conditions on SDS/PAGE. pI of LNCaP-PSA isoforms varied from 6.8 to 8.2. Pool A had the highest specific activity, 37 nmol/(min x mg). All the pools formed stable complexes with alpha1-antichymotrypsin and alpha2-macroglobulin. The pools contained 10-60% of N-terminally correctly processed LNCaP-PSA isoforms. According to the molecular modelling, the addition or deletion of two or four N-terminal amino acids could affect the three-dimensional structure and thereby remarkably reduce the enzyme activity of LNCaP-PSA.

摘要

为了表征癌细胞产生的前列腺特异性抗原（PSA），对人前列腺癌细胞LNCaP分泌的不同PSA异构体进行了纯化。LNCaP-PSA的产生由合成雄激素R1881诱导。LNCaP-PSA被分离成四个组分。在SDS/PAGE上，这些组分中LNCaP-PSA异构体在还原条件下的分子量为34 kDa，在非还原条件下为29 kDa。LNCaP-PSA异构体的pI在6.8至8.2之间变化。组分A具有最高的比活性，为37 nmol/（min·mg）。所有组分均与α1-抗糜蛋白酶和α2-巨球蛋白形成稳定的复合物。这些组分含有10-60%的N端正确加工的LNCaP-PSA异构体。根据分子建模，N端添加或缺失两个或四个氨基酸可能会影响三维结构，从而显著降低LNCaP-PSA的酶活性。