PMID- 21740816
OWN - NLM
STAT- MEDLINE
DCOM- 20111214
LR  - 20211203
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 124
IP  - 10
DP  - 2011 May
TI  - Menin expression is regulated by transforming growth factor beta signaling in 
      leukemia cells.
PG  - 1556-62
AB  - BACKGROUND: Menin is a ubiquitously expressed protein encoded by the multiple 
      endocrine neoplasia type 1 (MEN1) gene. Besides its importance in endocrine 
      organs, menin has been shown to interact with the mixed lineage leukemia (MLL) 
      protein, a histone H3 lysine 4 methyltransferase, and plays a critical role in 
      hematopoiesis and leukemogenesis. Previous studies have shown that menin promotes 
      transforming growth factor beta (TGF-beta) signaling in endocrine cells. However, 
      little is known regarding the impact of TGF-beta pathway on menin in hematopoietic 
      system. Here, with leukemia cell lines generated from conditional MEN1 or TGF-beta 
      receptor (TbetaRII) knockout mouse models, we investigated the possible cross-talk 
      of these two pathways in leukemia cells. METHODS: MEN1 or TbetaRII conditional 
      knockout mice were bred and the bone marrow cells were transduced with 
      retroviruses expressing oncogeneic MLL-AF9 (a mixed lineage leukemia fusion 
      protein) to generate two leukemia cell lines. Cell proliferation assays were 
      performed to investigate the effect of TGF-beta treatment on MLL-AF9 transformed 
      leukemia cells with/without MEN1 or TbetaRII excision. Menin protein was detected 
      with Western blotting and mRNA levels of cell proliferation-related genes Cyclin 
      A(2) and Cyclin E(2) were examined with real-time RT-PCR for each treated sample. 
      In vivo effect of TGF-beta signal on menin expression was also investigated in mouse 
      liver tissue after TbetaRII excision. RESULTS: TGF-beta not only inhibited the 
      proliferation of wild type MLL-AF9 transformed mouse bone marrow cells, but also 
      up-regulated menin expression in these cells. Moreover, TGF-beta failed to further 
      inhibit the proliferation of Men1-null cells as compared to Men1-expressing 
      control cells. Furthermore, excision of TbetaRII, a vital component in TGF-beta 
      signaling pathway, down-regulated menin expression in MLL-AF9 transformed mouse 
      bone marrow cells. In vivo data also confirmed that menin expression was 
      decreased in liver samples of conditional TbetaRII knockout mice after TbetaRII 
      excision. CONCLUSION: These results provided the first piece of evidence of 
      cross-talk between menin and TGF-beta signaling pathways in regulating proliferation 
      of leukemia cells, suggesting that manipulating the cross-talk of the two 
      pathways may lead to a novel therapy for leukemia.
FAU - Zhang, Hui
AU  - Zhang H
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Liu, Zu-Guo
AU  - Liu ZG
FAU - Hua, Xian-Xin
AU  - Hua XX
LA  - eng
GR  - R01-CA-100912/CA/NCI NIH HHS/United States
GR  - R01-CA-113962/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (MLL-AF9 fusion protein, mouse)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Humans
MH  - Leukemia/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/genetics/*metabolism
MH  - Oncogene Proteins, Fusion/genetics/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor, Transforming Growth Factor-beta Type II
MH  - Receptors, Transforming Growth Factor beta/genetics/*metabolism
MH  - Transforming Growth Factor beta/genetics/*metabolism
EDAT- 2011/07/12 06:00
MHDA- 2011/12/15 06:00
CRDT- 2011/07/12 06:00
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2011/12/15 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2011 May;124(10):1556-62.