PMID- 30911995
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20210331
IS  - 1532-2807 (Electronic)
IS  - 1219-4956 (Linking)
VI  - 26
IP  - 2
DP  - 2020 Apr
TI  - Attenuation of MAMLD1 Expression Suppresses the Growth and Migratory Properties 
      of Gonadotroph Pituitary Adenomas.
PG  - 937-946
LID - 10.1007/s12253-019-00615-2 [doi]
AB  - Gonadotroph pituitary adenomas (GPAs) constitute approximately 15-40% of 
      pituitary tumors. Some GPAs can be highly infiltrative, making full surgical 
      resection challenging and increasing the risk of recurrence. The transcriptional 
      co-activator Mastermind-Like Domain Containing 1 (MAMLD1, CXorf6, F18) is 
      involved in regulating signaling pathways important in pituitary tumorigenesis, 
      including the Notch signaling pathway. However, MAMLD1's role in GPA remains 
      unknown. GPA biopsies were collected from 96 patients following surgery, who were 
      monitored until tumor recurrence. GPA tissue was used for immunohistochemistry. 
      The murine GPA cell lines alphaT3 and LbetaT2 were used for in vitro experiments. 
      Lentiviral constructs were employed for MAMLD1 knockdown (KD) and dominant 
      negative (DN) mutant experiments. Quantitative real-time PCR (qPCR) and Western 
      blotting of MAMLD1 and Notch2 were performed. MTT and Transwell assays were used 
      to quantify proliferation and migration, respectively. An alphaT3 xenograft model was 
      established in athymic nude mice followed by fluorescent IHC of xenograft tumors. 
      MAMLD1 and Notch2 levels correlated positively with aggressive GPAs. Increased 
      MAMLD1 levels correlated with shortened recurrence-free survival (RFS) in 
      aggressive GPA patients. Moreover, MAMLD1 expression independently affected 
      patient RFS according to multivariate Cox regression. In vitro, MAMLD1 KD in the 
      murine GPA cell lines attenuated their proliferation and migration and Notch2 
      expression. Additionally, DN MAMLD1(L210X) lowered their proliferative and 
      migratory capacity. MAMLD1 KD suppressed tumor growth and Notch2 expression in 
      murine xenografts. MAMLD1 may serve as a predictor of GPA patient outcome and may 
      also be leveraged as a possible therapeutic target for aggressive GPA tumors.
FAU - Qi, Junhui
AU  - Qi J
AD  - Department of Neurosurgery, The Second Hospital of Yunnan Province, Kunming, 
      People's Republic of China.
FAU - Ni, Wei
AU  - Ni W
AD  - Department of Neurosurgery, The Third Affiliated Hospital of Kunming Medical 
      University, No. 519, Kunzhou Road, Kunming, Yunnan Province, 650118, People's 
      Republic of China. niweikm2018@163.com.
AD  - Department of Neurosurgery, Yunnan Cancer Hospital, Kunming, People's Republic of 
      China. niweikm2018@163.com.
LA  - eng
GR  - H-2017048/Medical Reserve Talent Training Project of Yunnan Province/
PT  - Journal Article
DEP - 20190325
PL  - Switzerland
TA  - Pathol Oncol Res
JT  - Pathology oncology research : POR
JID - 9706087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MAMLD1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adenoma/*pathology
MH  - Animals
MH  - Cell Movement/physiology
MH  - Cell Proliferation/physiology
MH  - DNA-Binding Proteins/*metabolism
MH  - Female
MH  - Gonadotrophs/metabolism
MH  - Heterografts
MH  - Humans
MH  - Male
MH  - Mice
MH  - Nuclear Proteins/*metabolism
MH  - Pituitary Neoplasms/*pathology
MH  - Transcription Factors/*metabolism
OTO - NOTNLM
OT  - CXorf6
OT  - MAMLD1
OT  - Notch
OT  - Pituitary adenoma
EDAT- 2019/03/27 06:00
MHDA- 2021/04/01 06:00
CRDT- 2019/03/27 06:00
PHST- 2018/12/07 00:00 [received]
PHST- 2019/02/08 00:00 [accepted]
PHST- 2019/03/27 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2019/03/27 06:00 [entrez]
AID - 10.1007/s12253-019-00615-2 [pii]
AID - 10.1007/s12253-019-00615-2 [doi]
PST - ppublish
SO  - Pathol Oncol Res. 2020 Apr;26(2):937-946. doi: 10.1007/s12253-019-00615-2. Epub 
      2019 Mar 25.