PMID- 20492406
OWN - NLM
STAT- MEDLINE
DCOM- 20100820
LR  - 20211203
IS  - 1447-0756 (Electronic)
IS  - 1341-8076 (Linking)
VI  - 36
IP  - 2
DP  - 2010 Apr
TI  - Granulosa cell tumor with activated mTOR-HIF-1alpha-VEGF pathway.
PG  - 448-53
LID - 10.1111/j.1447-0756.2009.01127.x [doi]
AB  - The DNA-binding activity of hypoxia-inducible factor-1 alpha (HIF-1alpha) has 
      been analyzed for various gynecological tumors. Among the tumors that were 
      studied, there was a finding of a high level of DNA-binding HIF-1alpha activity, 
      although it was limited to one case of adult type granulosa cell tumor (GCT). In 
      this case a 60-year-old female had marked immunohistochemical expression of 
      HIF-1alpha. The expressions of the mammalian target of rapamycin (mTOR) and 
      phosphorylated-mTOR (p-mTOR) were also marked, and vascular endothelial growth 
      factor (VEGF) was moderately expressed. To compare the expression profiles, 11 
      consecutive cases with adult type GCT were used. All cases showed marked 
      expressions of HIF-1alpha and mTOR, but p-mTOR expression was moderately to 
      markedly observed in four of the 12 cases. VEGF was expressed in all cases in 
      varying degrees. Based on the evidence that downregulation of the mTOR pathway 
      due to treatment with rapamycin (everolimus) would suppress tumor cell growth, an 
      experimental study using the GCT cell line was designed to clarify whether 
      HIF-1alpha and VEGF expressions decline. As a result, the expressions of p-mTOR, 
      HIF-1alpha and VEGF were suppressed, but those of mTOR were not. It was concluded 
      that mTOR-targeted therapy may represent a promising strategy for some GCT with 
      an activated mTOR-HIF-1alpha-VEGF pathway.
FAU - Miyazawa, Masaki
AU  - Miyazawa M
AD  - Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
FAU - Yasuda, Masanori
AU  - Yasuda M
FAU - Fujita, Mariko
AU  - Fujita M
FAU - Hirabayashi, Kenichi
AU  - Hirabayashi K
FAU - Hirasawa, Takeshi
AU  - Hirasawa T
FAU - Kajiwara, Hiroshi
AU  - Kajiwara H
FAU - Muramatsu, Toshinari
AU  - Muramatsu T
FAU - Miyazaki, Sayuri
AU  - Miyazaki S
FAU - Harasawa, Makiko
AU  - Harasawa M
FAU - Matsui, Naruaki
AU  - Matsui N
FAU - Ogane, Naoki
AU  - Ogane N
FAU - Murakami, Masaru
AU  - Murakami M
FAU - Mikami, Mikio
AU  - Mikami M
FAU - Yanase, Toshihiko
AU  - Yanase T
FAU - Osamura, R Yoshiyuki
AU  - Osamura RY
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - Australia
TA  - J Obstet Gynaecol Res
JT  - The journal of obstetrics and gynaecology research
JID - 9612761
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Female
MH  - Granulosa Cell Tumor/*metabolism/surgery
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Immunohistochemistry
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Middle Aged
MH  - Ovarian Neoplasms/*metabolism/surgery
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases
MH  - Vascular Endothelial Growth Factor A/*metabolism
EDAT- 2010/05/25 06:00
MHDA- 2010/08/21 06:00
CRDT- 2010/05/25 06:00
PHST- 2010/05/25 06:00 [entrez]
PHST- 2010/05/25 06:00 [pubmed]
PHST- 2010/08/21 06:00 [medline]
AID - JOG1127 [pii]
AID - 10.1111/j.1447-0756.2009.01127.x [doi]
PST - ppublish
SO  - J Obstet Gynaecol Res. 2010 Apr;36(2):448-53. doi: 
      10.1111/j.1447-0756.2009.01127.x.