Krockenberger M, Honig A, Rieger L, Coy J F, Sutterlin M, Kapp M, Horn E, Dietl J, Kammerer U
Department of Obstetrics and Gynecology, University of Wuerzburg, Josef-Schneider-Strasse 4, 97080 Wuerzburg, Germany.
Int J Gynecol Cancer. 2007 Jan-Feb;17(1):101-6. doi: 10.1111/j.1525-1438.2007.00799.x.
Tumorbiology of ovarian cancer remains unclear. However, it is known that ovarian tumors, especially carcinomas, show elevated expression of glucose membrane transporters for facilitated glucose uptake. It can be assumed that increased glucose uptake leads to higher glucose metabolism. The energy resources of fully malignant transformed carcinomas are mainly supplied by aerobic glycolysis, for which several pathways are known. A key role in aerobic glycolysis is described for the transketolase enzymes. Recently, a novel transketolase-like enzyme called transketolase-like 1 (TKTL1) has been described that links aerobic glycolysis to the synthesis of fatty acids via production of acetyl-CoA. In order to investigate the role of TKTL1 for the progression of ovarian carcinomas, we examined paraffin sections of normal ovarian tissues, ovarian borderline tumors, and mucinous or serous papillary ovarian adenocarcinomas with respect to their expression of TKTL1. We identified a significantly elevated expression of TKTL1 in serous papillary ovarian adenocarcinomas, which correlates with poor prognostic parameters in the examined study group. Therefore, it can be assumed that TKTL1 plays a crucial role in ovarian cancer metabolism and that its expression predicts poor prognosis. Further investigations should be performed in order to evaluate whether this new enzyme is important for ovarian cancer tumorbiology and to analyze the potential role of TKTL1 as new target for specific antitumoral therapy.
卵巢癌的肿瘤生物学仍不清楚。然而,已知卵巢肿瘤,尤其是癌,会表现出促进葡萄糖摄取的葡萄糖膜转运蛋白表达升高。可以推测,葡萄糖摄取增加会导致更高的葡萄糖代谢。完全恶性转化的癌的能量来源主要由有氧糖酵解提供,对此有几种已知途径。转酮醇酶在有氧糖酵解中起关键作用。最近,一种名为转酮醇酶样1(TKTL1)的新型转酮醇酶样酶被发现,它通过产生乙酰辅酶A将有氧糖酵解与脂肪酸合成联系起来。为了研究TKTL1在卵巢癌进展中的作用,我们检查了正常卵巢组织、卵巢交界性肿瘤以及黏液性或浆液性乳头状卵巢腺癌的石蜡切片中TKTL1的表达情况。我们发现浆液性乳头状卵巢腺癌中TKTL1的表达显著升高,这与所研究的患者组中不良预后参数相关。因此,可以推测TKTL1在卵巢癌代谢中起关键作用,其表达预示着预后不良。应进行进一步研究,以评估这种新酶对卵巢癌肿瘤生物学是否重要,并分析TKTL1作为特异性抗肿瘤治疗新靶点的潜在作用。