Wang Ruoxiang, Xu Jianchun, Mabjeesh Nicola, Zhu Guodong, Zhou Jianguang, Amin Mahul, He Dalin, Marshall Fray F, Zhau Haiyen E, Chung Leland W K
Department of Urology and Pathology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Clin Cancer Res. 2007 Oct 15;13(20):6040-8. doi: 10.1158/1078-0432.CCR-07-0640.
We previously reported the isolation and characterization of PrLZ, a novel prostate-specific and androgen-responsive gene of the tumor protein D52 family at chromosome 8q21.1. PrLZ is the only known gene in this locus with prostate specificity. Expression level of PrLZ was elevated specifically in cancer cells, suggesting its association with malignancy.
To define its biological function in the morphogenesis, development, and functional maturation of the prostate gland and to gain further insight into its role in prostate cancer, we examined PrLZ expression in prostate specimens during early embryonic development and in adult tissue.
PrLZ first appears in the nuclei of the prostate epithelia at 16 weeks of gestation before its distribution in the cytoplasm at later ages. Its expression peaks at 24 years of age, declines at 31 years of age, and maintains a minimal level in later age. On prostate cancer development, PrLZ expression is reactivated, and its expression increases from primary localized tumor to bone metastasis. Overexpression of PrLZ in prostate cancer cells accelerates their growth in vitro and tumor formation in vivo.
This work identifies PrLZ as a marker for prostate cancer progression and metastasis, and its pattern of expression is suggestive of a proto-oncogene.
我们之前报道了PrLZ的分离与特性,它是位于8号染色体q21.1区域的肿瘤蛋白D52家族中一个新的前列腺特异性且雄激素应答性基因。PrLZ是该位点唯一已知的具有前列腺特异性的基因。PrLZ的表达水平在癌细胞中特异性升高,提示其与恶性肿瘤相关。
为了确定其在前列腺腺管形态发生、发育及功能成熟中的生物学功能,并进一步深入了解其在前列腺癌中的作用,我们检测了PrLZ在胚胎早期发育及成年组织的前列腺标本中的表达。
PrLZ在妊娠16周时首次出现在前列腺上皮细胞核中,之后在细胞质中分布。其表达在24岁时达到峰值,31岁时下降,并在之后维持在最低水平。在前列腺癌发生过程中,PrLZ表达重新激活,且其表达从原发性局限性肿瘤到骨转移逐渐增加。在前列腺癌细胞中过表达PrLZ可加速其体外生长及体内肿瘤形成。
本研究确定PrLZ为前列腺癌进展和转移的标志物,其表达模式提示它是一种原癌基因。