PMID- 15301716
OWN - NLM
STAT- MEDLINE
DCOM- 20050125
LR  - 20150313
VI  - 23
IP  - 8
DP  - 2004 Aug
TI  - [Effects of lovastatin on cell cycle distribution in MCF-7 cells transfected with 
      BRCA1].
PG  - 924-8
AB  - BACKGROUND & OBJECTIVE: The breast and ovarian cancer susceptibility gene BRCA1 
      acts as a tumor suppressor gene, its product expresses in a cell cycle-dependent 
      manner. Inheritance of a mutant allele of BRCA1 leads to increased risk of 
      developing breast,and ovarian cancers. Lovastatin, as a potent inhibitor of 
      3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase),is the main 
      rate-limiting enzyme of endogenous cholesterol biosynthesis pathway. This study 
      was to evaluate the effect and mechanism of combined application of BRCA1 and 
      lovastatin on cell cycle distribution of MCF-7 cells. METHODS: MCF-7 cells were 
      transfected with expression vector pcDNA3-beta-HA-hsBRCA1 containing full-length 
      BRCA1, and named MCF-7BRCA1 cells. The expression of BRCA1 gene was examined with 
      reverse transcription polymerase chain reaction (RT-PCR) and Western blot 
      analysis. After cultured with 8 micromol/L lovastatin, growth curve and MTT assay 
      were used to determine cell proliferation capacity; the cell cycle distribution 
      was measured with flow cytometry (FCM). Meanwhile,the protein expression of 
      Cyclin D1 and retinoblastoma (Rb) were analyzed by Western blot analysis. 
      RESULTS: The pcDNA3-beta-HA-hsBRCA1 plasmids were successfully transfected into 
      MCF-7 cells and expressed stably. The growth curve and MTT assay results showed 
      that cell proliferation capacity decreased in the cells cultured with lovastatin 
      for 4 days. FCM showed that S phase, and G2/M phase of BRCA1-infected cells 
      decreased,while G0/G1 phase increased after cultured with lovastatin, the cells 
      were blocked in G0/G1 phase at 72 h post-treatment by lovastatin. Ectopic 
      expression of BRCA1 leads to decrease of the Rb protein and Cyclin D1 protein. 
      Overall data showed that the effects of Lovastatin were more obviously in 
      MCF-7BRCA1 cells than MCF-7 cells. CONCLUSIONS: Overexpression of BRCA1 protein 
      may amplify sensibility of breast cancer to lovastatin,and enhance the anti-tumor 
      effect of lovastatin.
FAU - Luo, Yuan-Qiong
AU  - Luo YQ
AD  - Department of Nutrition Hygiene, Faculty of Preventive Medicine, The Third 
      Military Medical University, Chongqing, 400038, PR China.
FAU - Mi, Man-Tian
AU  - Mi MT
FAU - Wei, Na
AU  - Wei N
FAU - Xu, Hong-Xia
AU  - Xu HX
FAU - Zhu, Jun-Dong
AU  - Zhu JD
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Ai Zheng
JT  - Ai zheng = Aizheng = Chinese journal of cancer
JID - 9424852
RN  - 0 (Antineoplastic Agents)
RN  - 0 (BRCA1 Protein)
RN  - 0 (Retinoblastoma Protein)
RN  - 136601-57-5 (Cyclin D1)
RN  - 9LHU78OQFD (Lovastatin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - BRCA1 Protein/*biosynthesis/genetics
MH  - Breast Neoplasms/metabolism/*pathology
MH  - Cell Cycle/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cyclin D1/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genes, BRCA1
MH  - Genetic Vectors
MH  - Humans
MH  - Lovastatin/*pharmacology
MH  - Retinoblastoma Protein/metabolism
MH  - Transfection
EDAT- 2004/08/11 05:00
MHDA- 2005/01/26 09:00
CRDT- 2004/08/11 05:00
PHST- 2004/08/11 05:00 [pubmed]
PHST- 2005/01/26 09:00 [medline]
PHST- 2004/08/11 05:00 [entrez]
AID - 1000467X2004080924 [pii]
PST - ppublish
SO  - Ai Zheng. 2004 Aug;23(8):924-8.