PMID- 25175341
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20141017
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 32
IP  - 5
DP  - 2014 Nov
TI  - Downregulated Chibby in laryngeal squamous cell carcinoma with increased 
      expression in laryngeal carcinoma Hep-2 cells.
PG  - 1947-56
LID - 10.3892/or.2014.3451 [doi]
AB  - Chibby (Cby) inhibits Wnt/beta-catenin-mediated transcriptional activation by 
      competing with Lef-1 (the transcription factor and target of beta-catenin) to bind 
      to beta-catenin. This suggests that Cby could be a tumor suppressor protein. In the 
      present study, we examined Cby expression in laryngeal squamous cell carcinoma 
      (LSCC) and its function and mechanism in laryngeal carcinoma cell lines. Cby 
      expression levels were investigated by immunohistochemistry in a panel of 36 LSCC 
      patient cases. The expression of beta-catenin, c-myc and cyclin D1 in Hep-2 were 
      determined through RT-PCR and western blot analysis. Activity of Wnt/beta-catenin 
      signaling pathway after overexpression of Cby was measured by TCF/LEF luciferase 
      reporter gene assay. Proliferation, clone forming ability, cell cycle 
      distribution and cell apoptosis of Hep-2 cells were detected by MTT assay, plate 
      colony forming assay, flow cytometry and TUNEL assay, respectively. This study 
      showed that expression of Cby protein was strongly downregulated in LSCC tumor 
      tissues in comparison to normal laryngeal mucosa samples. No significant 
      correlation was found between the expression of Cby in tumor tissue and gender, 
      age, clinical stage and tumor differentiation of laryngeal cancer patients. When 
      Cby was overexpressed in Hep-2 cells, the expression of cyclin D1 was reduced and 
      beta-catenin activity was inhibited. Proliferation and plate colony forming assays 
      revealed a significant inhibitory effect of Cby on growth and colony formation 
      ability of Hep-2 cells after Cby overexpression in comparison to control and 
      mock-infected cells. In addition, we also found that upregulated expression of 
      Cby resulted in accumulation of numbers of cells in G0/G1 phase with concomitant 
      decrease in S phase by cell cycle assay. TUNEL staining demonstrated that, 
      compared with the control group, the rate of apoptosis in the plv-cs2.0-Cby group 
      was significantly increased. Taken together, downregulation of Cby was observed 
      in LSCC, but with no significant correlation to the clinicopathological features 
      of LSCC patients. Overexpression of Cby effectively suppressed laryngeal 
      carcinoma cell growth and promoted its apoptosis. A better understanding of the 
      mechanisms of Cby gene activation in LSCC could provide potential novel 
      therapeutic targets for human laryngeal carcinoma.
FAU - Xu, Jue
AU  - Xu J
AD  - Department of Otolaryngology, The First Hospital Affiliated to Huzhou University 
      Medical College, Huzhou, Zhejiang 313000, P.R. China.
FAU - Ren, Gang
AU  - Ren G
AD  - Department of Otolaryngology, The First Hospital Affiliated to Huzhou University 
      Medical College, Huzhou, Zhejiang 313000, P.R. China.
FAU - Zhao, De-An
AU  - Zhao DA
AD  - Department of Otolaryngology, the 174th Hospital of PLA, Xiamen, Fujian 361003, 
      P.R. China.
FAU - Li, Bo-An
AU  - Li BA
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen 
      University, Xiamen, Fujian, P.R. China.
FAU - Cai, Cheng-Fu
AU  - Cai CF
AD  - Department of Otolaryngology, The First Affiliated Hospital of Xiamen University, 
      Xiamen, Fujian 361003, P.R. China.
FAU - Zhou, Yi
AU  - Zhou Y
AD  - Department of Otolaryngology, The First Affiliated Hospital of Xiamen University, 
      Xiamen, Fujian 361003, P.R. China.
FAU - Luo, Xian-Yang
AU  - Luo XY
AD  - Department of Otolaryngology, The First Affiliated Hospital of Xiamen University, 
      Xiamen, Fujian 361003, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140829
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (CBY1 protein, human)
RN  - 0 (CCND1 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apoptosis
MH  - Carcinoma, Squamous Cell/*metabolism/pathology
MH  - Carrier Proteins/*genetics/*metabolism
MH  - Cyclin D1/metabolism
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Hep G2 Cells
MH  - Humans
MH  - Laryngeal Neoplasms/*metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Nuclear Proteins/*genetics/*metabolism
MH  - Wnt Signaling Pathway
EDAT- 2014/09/02 06:00
MHDA- 2015/10/27 06:00
CRDT- 2014/09/02 06:00
PHST- 2014/06/12 00:00 [received]
PHST- 2014/08/03 00:00 [accepted]
PHST- 2014/09/02 06:00 [entrez]
PHST- 2014/09/02 06:00 [pubmed]
PHST- 2015/10/27 06:00 [medline]
AID - 10.3892/or.2014.3451 [doi]
PST - ppublish
SO  - Oncol Rep. 2014 Nov;32(5):1947-56. doi: 10.3892/or.2014.3451. Epub 2014 Aug 29.