MS4A8B promotes cell proliferation in prostate cancer.
BACKGROUND
Prostate cancer cells must maintain or achieve the further ability of proliferation during the progression. The molecular mechanisms, however, remain poorly understood. We identified a novel oncogene, termed membrane-spanning 4-domains, subfamily A, member 8B (MS4A8B), over-expressed in prostate cancer.


METHODS
We firstly detected MS4A8B mRNA in 13 types of paired human normal and cancer tissues by real-time polymerase chain reaction (RT-PCR). In 140 clinically localized prostate cancer samples from radical prostatectomy, immunohistochemical staining was performed to study MS4A8B and PCNA protein level as an index of proliferative activity, TUNEL staining as an index of apoptosis. As MS4A8B RNAi and cDNA transfection technologies were used, the effect of MS4A8B on cellular vitality was determined in vitro and in vivo.


RESULTS
MS4A8B mRNA was over-expressed specifically in prostate cancer. Positive ratios of MS4A8B protein expression were 1.94%, 5.92%, and 62.8% in benign, HPIN and prostate cancer, respectively. Moreover, MS4A8B was positively associated with Gleason score, the proliferation index. In vitro, MS4A8B knockdown resulted in G1 -S cell cycle arrest and descended vitality, MS4A8B over-expression with accelerated S phase entry, elevated vitality in prostate cancer cells. Moreover, it was also found that expression of MS4A8B led to changes of Cyclin D1 , Cyclin E1 and PCNA. LNCaP cells transfected with sh-MS4A8B lentivirus particles grew more slowly when subcutaneously injected into the flanks of nude mice.


CONCLUSIONS
We conclude that the expression of MS4A8B expression promotes cell proliferation and plays an important role in carcinogenesis and progression of prostate cancer.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Lin
L
Ye
Xu-Dong
XD
Yao
Fang-Ning
FN
Wan
Yuan-Yuan
YY
Qu
Zhi-Yu
ZY
Liu
Xu-Xia
XX
Shen
Sheng
S
Li
Xiao-Jun
XJ
Liu
Feng
F
Yue
Na
N
Wang
Bo
B
Dai
Ding-Wei
DW
Ye
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric
C438731:MS4A7 protein, human; D008565:Membrane Proteins; D012334:RNA, Neoplasm; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
MS4A8B; cell cycle; proliferation; prostate cancer