Kinoshita H, Ogawa O, Mitsumori K, Kakehi Y, Terachi T, Yoshida O
Department of Urology, Faculty of Medicine, Kyoto University, Japan.
J Urol. 1998 Jan;159(1):245-51. doi: 10.1016/s0022-5347(01)64076-x.
In malignant tumors, telomerase reactivation plays an important role in the acquisition of cellular immortality. We evaluated the telomerase activity in renal cell carcinomas (RCCs) with special reference to their clinicopathologic features.
Telomerase activity was examined in 47 RCCs and 9 RCC cell lines by telomeric repeat amplification protocol assay (TRAP). The telomere lengths were assessed by Southern analysis of terminal restriction fragments (TRFs) generated by Hinfl-digested DNA.
Thirty-six (77%) of the 47 RCCs and all 9 RCC cell lines showed telomerase activity, whereas no activity was detected in any of 30 normal kidneys. When the tumors were histopathologically classified, only one (17%) of the 6 chromophobe cell carcinomas was telomerase-positive. This frequency was significantly low (p < 0.001) when compared with those in clear cell RCCs (93%; 26/28). In 40 of the 47 patients, DNA from the tumor tissues and the paired normal kidneys was available for analysis of the TRF lengths. No tumor showed elongated TRF length compared to its paired normal kidney. Regarding the relationship between telomere length and telomerase activity, 23 (74%) of the 31 telomerase-positive RCC and 6 (67%) of the 9 telomerase-negative RCC exhibited reduced TRF. There was no significant correlation between the telomere reduction and telomerase activity.
The mechanism for preventing telomere shortening may differ according to RCC subtype. Alternatively, telomerase-negative tumors may have yet to reach the immortal stage when they progress to clinical cancer. The telomerase activity status may contribute to the biological potential and the prognosis of RCCs.
在恶性肿瘤中，端粒酶重新激活在细胞永生化过程中起重要作用。我们评估了肾细胞癌（RCC）中端粒酶活性，并特别参考了其临床病理特征。
采用端粒重复序列扩增协议分析（TRAP）检测了47例RCC和9种RCC细胞系中的端粒酶活性。通过对经Hinfl消化的DNA产生的末端限制片段（TRF）进行Southern分析来评估端粒长度。
47例RCC中的36例（77%）和所有9种RCC细胞系均显示端粒酶活性，而30例正常肾脏中均未检测到活性。当对肿瘤进行组织病理学分类时，6例嫌色细胞癌中只有1例（17%）端粒酶呈阳性。与透明细胞RCC（93%；26/28）相比，该频率显著较低（p<0.001）。47例患者中的40例，其肿瘤组织和配对正常肾脏的DNA可用于TRF长度分析。与配对的正常肾脏相比，没有肿瘤显示TRF长度延长。关于端粒长度与端粒酶活性之间的关系，31例端粒酶阳性RCC中的23例（74%）和9例端粒酶阴性RCC中的6例（67%）表现出TRF缩短。端粒缩短与端粒酶活性之间无显著相关性。
根据RCC亚型，防止端粒缩短的机制可能不同。或者，端粒酶阴性肿瘤在进展为临床癌症时可能尚未达到永生化阶段。端粒酶活性状态可能有助于RCC的生物学潜能和预后。
