Compensatory alterations in energy homeostasis characterized in uterine tumors from hereditary leiomyomatosis and renal cell cancer

被引:11
作者
Catherino, William H.
Mayers, Chantal M.
Mantzouris, Tammy
Armstrong, Alicia Y.
Linehan, Marston
Segars, James H.
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA
[2] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA
[3] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA
关键词
hereditary leiomyomatosis and renal cell cancer; fumarate hydratase; leiomyoma; glycolysis; enolase; aldolase; pyruvate kinase; Krebs cycle;
D O I
10.1016/j.fertnstert.2006.11.198
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: To determine the molecular alterations that maintain energy homeostasis in hereditary leiomyomatosis and renal cell cancer (HLRCC) uterine tumors with disrupted fumarate hydratase, compared with nonsyndromic uterine tumors. Design: Laboratory study. Setting: Tertiary academic university hospital. Patient(S): Eleven nonsyndromic leiomyoma-myometrium pairs and three HLRCC leiomyoma-myometrium pairs were obtained from patients who were recruited at national and military research centers in the United States. Intervention(s): Molecular analysis. Main Outcome Measure(S): Hereditary leiomyomatosis and renal cell cancer and nonsyndromic leiomyomas were compared with patient-matched myometrium for relative glycolysis and Krebs cycle gene expression. Result(s): By microarray analysis, we confirmed that fumarate hydratase messenger RNA (mRNA) was underexpressed in HLRCC fibroids, compared with matched myometrium. Consistent with the possibility that alterations in fumarate hydratase represented a change to a more anaerobic state, we found that HLRCC fibroids overexpressed genes such as phosphofructokinase, aldolase, phosphoglycerate kinase, enolase, and pyruvate kinase. Ex pression of these genes was not altered in nonsyndromic leiomyomas. Furthermore, there were no overt changes in expression of Krebs cycle enzyme gene expression, with the exception of fumarate hydratase. Conclusion(s): Our findings demonstrate that alterations in fumarate hydratase are compensated for by increases in glycolysis enzyme expression in HLRCC. (C)2007 by American Society for Reproductive Medicine.
引用
收藏
页码:1039 / 1048
页数:10
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