PMID- 24420924
OWN - NLM
STAT- MEDLINE
DCOM- 20140923
LR  - 20211021
IS  - 1573-7373 (Electronic)
IS  - 0167-594X (Linking)
VI  - 116
IP  - 3
DP  - 2014 Feb
TI  - CUL4A is overexpressed in human pituitary adenomas and regulates pituitary tumor 
      cell proliferation.
PG  - 625-32
LID - 10.1007/s11060-013-1349-2 [doi]
AB  - Cullin 4A (CUL4A) encodes a core subunit of an E3 ubiquitin ligase that targets 
      proteins for ubiquitin-mediated degradation, and aberrant expression of the CUL4A 
      is found in many tumor types. However, its roles and clinicopathologic 
      significance in pituitary adenomas are not clear. The aim of this study was to 
      investigate the possible role of CUL4A in pituitary tumorigenesis. 
      Immunohistochemistry was used to examine CUL4A expression in human normal 
      pituitaries and pituitary tumors with respect to various clinicopathologic 
      factors in pituitary adenomas. Cell proliferation was assessed by MTT and colony 
      formation, and migration and invasion were analyzed by Transwell and Matrigel 
      assays after CUL4A overexpression or knockdown in pituitary tumor cells. 
      Overexpression of CUL4A was frequently observed in pituitary adenomas compared 
      with normal adenohypophysial tissue and significantly associated with tumor 
      progressiveness and invasion. CUL4A overexpression in GH3 adenoma cells increased 
      colony numbers, cell viability and cell invasion and silencing CUL4A in AtT20 
      adenoma cells decreased cell proliferation, migration and invasion. 
      Mechanistically, CUL4A could modulate the expression of p53, p21, and p27 in 
      pituitary tumor cells. In addition, high levels of CUL4A expression also 
      significantly inversely correlated with the p53 protein level in human pituitary 
      adenomas. Our results indicate that CUL4A enhances pituitary cell proliferation, 
      migration and invasion and may thus contribute to pituitary tumor development and 
      progression.
FAU - Xu, Yangyang
AU  - Xu Y
AD  - Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of 
      Education, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, 
      250012, Shandong, China.
FAU - Wang, Yunshan
AU  - Wang Y
FAU - Ma, Guangxin
AU  - Ma G
FAU - Wang, Qin
AU  - Wang Q
FAU - Wei, Guangwei
AU  - Wei G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140114
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (CUL4A protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9002-62-4 (Prolactin)
RN  - 9002-72-6 (Growth Hormone)
SB  - IM
MH  - Adenoma/*metabolism/pathology
MH  - Adrenocorticotropic Hormone/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cullin Proteins/genetics/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Growth Hormone/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Pituitary Neoplasms/*metabolism/pathology
MH  - Prolactin/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Retrospective Studies
MH  - Time Factors
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/metabolism
EDAT- 2014/01/15 06:00
MHDA- 2014/09/24 06:00
CRDT- 2014/01/15 06:00
PHST- 2013/06/22 00:00 [received]
PHST- 2013/12/29 00:00 [accepted]
PHST- 2014/01/15 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2014/09/24 06:00 [medline]
AID - 10.1007/s11060-013-1349-2 [doi]
PST - ppublish
SO  - J Neurooncol. 2014 Feb;116(3):625-32. doi: 10.1007/s11060-013-1349-2. Epub 2014 
      Jan 14.