Overexpression of cyclin L2 induces apoptosis and cell-cycle arrest in human lung cancer cells.
BACKGROUND
Uncontrolled cell division is one of the hallmarks of tumor growth. Researches have been focused on numerous molecules involved in this process. Cyclins are critical regulatory proteins of cell cycle progression and/or transcription. The present study aimed to investigate the anti-proliferative effect of cyclin L2, and to define its growth regulatory mechanisms using human lung adenocarcinoma cell line A549.


METHODS
Human cyclin L2 was transfected into human lung adenocarcinoma cells (A549 cell), and was expressed in a mammalian expression vector pcDNA3.1. The effects and mechanisms of the cyclin L2 in cell growth, cell cycle analysis and apoptosis were studied by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry or Western blot, respectively.


RESULTS
Overexpression of cyclin L2 inhibited the growth of A549 cells. Cell cycle analysis in cells transfected with pCCNL2 revealed an increment in proportion in G0/G1 phase ((68.07 +/- 4.2)%) in contrast to (60.39 +/- 2.82)% of the cells transfected with mock vector. Apoptosis occurred in (7.25 +/- 0.98)% cells transfected with pCCNL2, as compared with (1.25 +/- 0.21)% of the mock vector control group. Cyclin L2-induced-G0/G1 arrest and apoptosis involved upregulation of caspase-3 and downregulation of Bcl-2 and survivin.


CONCLUSIONS
The results indicate that overexpression of cyclin L2 protein may promote efficient growth inhibition of human lung adenocarcinoma cells by inducing G0/G1 cell cycle arrest and apoptosis.
Li
Hong-li
HL
Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
Wang
Tong-shan
TS
Li
Xiao-yu
XY
Li
Nan
N
Huang
Ding-zhi
DZ
Chen
Qi
Q
Ba
Yi
Y
D017209:Apoptosis; D053148:Caspase 3 / Q000096:biosynthesis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection
C483080:CCNL2 protein, human; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D053148:Caspase 3