Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA.
Int J Oncol. 2010 Dec;37(6):1477-82. doi: 10.3892/ijo_00000800.
Research into molecular and genetic mechanisms underlying prostate carcinogenesis in high-risk African American men would be greatly advanced by in vitro models of African American prostate tumors representing primary tumors. However, the generation of immortalized primary African American prostate cancer cells that will accurately reflect the in situ characteristics of malignant epithelium is currently limited but is greatly needed. We have successfully established immortalized cell lines of a pair of non-malignant and malignant tumors derived from an African American prostate cancer patient with HPV-16E6E7 (RC-77N/E and RC-77T/E). RC-77N/E and RC-77T/E cells are currently growing well at passage 40. Both cells exhibit epithelial morphology and are androgen sensitive. The RC-77T/E cells produced tumors in SCID mice whereas the RC-77N/E cells produced no tumor in SCID mice. These cells expressed androgen-regulated prostate-specific homobox gene, NKX 3.1, epithelial cell specific cytokeratn 8, androgen receptor (AR), prostate specific antigen (PSA), and p16. Chromosome analysis showed that both cell lines are similar; near diploid human male (XY) with most chromosome counts in the 45-48 range. However, RC-77T/E cell line has new marker chromosomes: M1B=del/t(4;?)(q28;?), M5=16q+ in addition to those observed in the RC-77N/E cell line (M1=del(4)(q28q34)+hsr in some, M1A=t(4q;?),M2=der(9?),M2A=del(M2p-),M3=iso(?), M4=der(22?)). This is the first documented case of the establishment of pair of non-malignant and malignant tumors derived from an African American prostate cancer patient. These models will provide novel tools to study the molecular and genetic mechanisms of prostate carcinogenesis, especially for high-risk African American men.
研究高危非裔美国男性前列腺癌发生的分子和遗传机制,将通过代表原发性肿瘤的非裔美国人前列腺肿瘤的体外模型得到极大推进。然而,目前生成能够准确反映恶性上皮原位特征的永生性非裔美国人前列腺癌细胞的能力受到很大限制,但又非常必要。我们已经成功建立了一对源自携带 HPV-16E6E7 的非裔美国人前列腺癌患者的非恶性和恶性肿瘤的永生化细胞系 RC-77N/E 和 RC-77T/E。RC-77N/E 和 RC-77T/E 细胞目前在传代 40 代时仍生长良好。这两种细胞均表现出上皮形态且对雄激素敏感。RC-77T/E 细胞在 SCID 小鼠中产生肿瘤,而 RC-77N/E 细胞在 SCID 小鼠中不产生肿瘤。这些细胞表达雄激素调节的前列腺特异性同源盒基因 NKX3.1、上皮细胞特异性细胞角蛋白 8、雄激素受体 (AR)、前列腺特异性抗原 (PSA) 和 p16。染色体分析显示这两种细胞系相似;接近二倍体人类男性(XY),大多数染色体计数在 45-48 范围内。然而,RC-77T/E 细胞系具有新的标记染色体:M1B=del/t(4;?)(q28;?),M5=16q+,除了在 RC-77N/E 细胞系中观察到的那些染色体(M1=del(4)(q28q34)+hsr 在某些情况下,M1A=t(4q;?),M2=der(9?),M2A=del(M2p-),M3=iso(?),M4=der(22?))。这是首例建立源自非裔美国人前列腺癌患者的非恶性和恶性肿瘤对的报道。这些模型将为研究前列腺癌发生的分子和遗传机制提供新的工具,特别是对于高危非裔美国人男性。