Jing Chun, El-Ghany Manal Abd, Beesley Carol, Foster Christopher S, Rudland Philip S, Smith Paul, Ke Youqiang
Department of Pathology, Faculty of Medicine, University of Liverpool, UK.
J Natl Cancer Inst. 2002 Apr 3;94(7):482-90. doi: 10.1093/jnci/94.7.482.
Prostate cancer is the most common noncutaneous male cancer and one of the least understood malignant diseases. Identifying key genetic factors involved in the metastasis of prostate cancer cells is critical. In this study, we used selective subtractive differential gene display to identify a gene whose decreased expression may contribute to the growth and expansion of prostate cancer.
We used 192 primer pair combinations and polymerase chain reaction technology to identify genes expressed in the benign prostate cell line PNT-2 but not in the malignant prostate cancer cell lines LNCaP, Du-145, PC-3, or PC-3M. The tazarotene-induced gene 1 (TIG1) was chosen for further study. TIG1 expression in normal tissues and cell lines was analyzed by northern blot and in normal and tumor prostate tissue sections by in situ hybridization. The in vitro invasiveness (migration through extracellular matrix) and in vivo tumorigenicity (growth in nude mice) were assessed for the highly malignant PC-3M cell line transfected with TIG1 or control cDNA. All statistical tests were two-sided.
TIG1 mRNA was expressed in a variety of normal tissues other than prostate tissue. TIG1 mRNA was detected in all 10 normal human prostate tissues and all 51 benign prostatic hyperplastic tissues analyzed but in only four of 51 malignant prostate tissues analyzed. Compared with vector-transfected cells, transfection of PC-3M cells with TIG1 decreased in vitro invasiveness from 14.7% to 3.7%, (mean difference = 11%; 95% confidence interval [CI] = 9.2% to 12.8%, P<.001) and decreased in vivo tumorigenicity from an average tumor weight of 1.31 g to 0.55 g, (mean difference = 0.76 g; 95% CI = 0.43 to 1.09 g, P<.001).
TIG1 may be a tumor suppressor gene whose diminished expression is involved in the malignant progression of prostate cancer.
前列腺癌是最常见的非皮肤性男性癌症，也是了解最少的恶性疾病之一。确定参与前列腺癌细胞转移的关键基因因素至关重要。在本研究中，我们使用选择性消减差异基因显示技术来鉴定一个基因，其表达降低可能有助于前列腺癌的生长和扩散。
我们使用192对引物组合和聚合酶链反应技术来鉴定在良性前列腺细胞系PNT-2中表达但在恶性前列腺癌细胞系LNCaP、Du-145、PC-3或PC-3M中不表达的基因。选择维甲酸诱导基因1（TIG1）进行进一步研究。通过Northern印迹分析正常组织和细胞系中的TIG1表达，并通过原位杂交分析正常和肿瘤前列腺组织切片中的TIG1表达。对用TIG1或对照cDNA转染的高恶性PC-3M细胞系评估其体外侵袭性（穿过细胞外基质的迁移）和体内致瘤性（在裸鼠中生长）。所有统计检验均为双侧检验。
TIG1 mRNA在除前列腺组织外的多种正常组织中表达。在所分析的所有10个正常人类前列腺组织和所有51个良性前列腺增生组织中均检测到TIG1 mRNA，但在所分析的51个恶性前列腺组织中仅在4个中检测到。与载体转染细胞相比，用TIG1转染PC-3M细胞可使体外侵袭性从14.7%降至3.7%，（平均差异=11%；95%置信区间[CI]=9.2%至12.8%，P<0.001），并使体内致瘤性从平均肿瘤重量1.31 g降至0.55 g，（平均差异=0.76 g；95%CI=0.43至1.09 g，P<0.001）。
TIG1可能是一种肿瘤抑制基因，其表达减少与前列腺癌的恶性进展有关。
