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


METHODS
Laboratory study.


METHODS
Tertiary academic university hospital.


METHODS
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.


METHODS
Molecular analysis.


METHODS
Hereditary leiomyomatosis and renal cell cancer and nonsyndromic leiomyomas were compared with patient-matched myometrium for relative glycolysis and Krebs cycle gene expression.


RESULTS
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. Expression 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.


CONCLUSIONS
Our findings demonstrate that alterations in fumarate hydratase are compensated for by increases in glycolysis enzyme expression in HLRCC.
Catherino
William H
WH
Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA. catheriw@mail.nih.gov
Mayers
Chantal M
CM
Mantzouris
Tammy
T
Armstrong
Alicia Y
AY
Linehan
W Marston
WM
Segars
James H
JH
D000328:Adult; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D018231:Leiomyomatosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology