PMID- 19610065
OWN - NLM
STAT- MEDLINE
DCOM- 20091106
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 125
IP  - 11
DP  - 2009 Dec 1
TI  - Annexin-A7 protects normal prostate cells and induces distinct patterns of 
      RB-associated cytotoxicity in androgen-sensitive and -resistant prostate cancer 
      cells.
PG  - 2528-39
LID - 10.1002/ijc.24592 [doi]
AB  - The tumor suppressor role of annexin-A7 (ANXA7) was previously demonstrated by 
      cancer susceptibility in Anxa7(+/-)-mice and by ANXA7 loss in human cancers, 
      especially in hormone-resistant prostate tumors. To gain mechanistic insights 
      into ANXA7 tumor suppression, we undertook an in vitro study in which we compared 
      wild-type (WT)-ANXA7 and dominant-negative (DN)-ANXA7 effects to a conventional 
      tumor suppressor p53 in prostate cancer cells with different androgen 
      sensitivity. Unlike p53 (which caused cell growth arrest and apoptosis to a 
      noticeable extent in benign PrEC), WT-ANXA7 demonstrated profound cytotoxicityin 
      androgen-sensitive LNCaP as well as in the androgen-resistant DU145 and PC3 
      prostate cancer cells, but not in PrEC. In androgen-sensitive LNCaP, WT-ANXA7 
      decreased low-molecular-weight (LMW) AR protein forms and maintained higher 
      retinoblastoma 1 (RB1)/phospho-RB1 ratio. In contrast, DN-ANXA7 (which lacks 
      phosphatidylserine liposome aggregation properties) increased LMW-AR forms and 
      hyperphosphorylated RB1 that was consistent with the lack of DN-ANXA7 
      cytotoxicity. According to the microarray-based Ingenuity Pathways Analysis, a 
      major WT-ANXA7 effect in androgen-sensitive LNCaP constituted of upregulation of 
      the RB1-binding transcription factor E2F1 along with its downstream proapoptotic 
      targets such as ASK1 and ASPP2. These results suggested a reversal of the 
      RBdependent repression of the proapoptotic E2F-mediated transcription. However, 
      DN-ANXA7 increased RB1/2 (but not E2F1) expression and induced the 
      proliferation-promoting ERK5, thereby maintaining the RB-dependent repression of 
      E2F-mediated apoptosis in LNcaP. On the other hand, in androgen-resistant cells, 
      WT-ANXA7 tumor suppressor effects involved PTEN and NFkB pathways. Thus, ANXA7 
      revived the RB-associated cell survival control and overcame androgen resistance 
      and dysfunctional status of major tumor suppressors commonly mutated in prostate 
      cancer. Published 2009 UICC.
FAU - Torosyan, Yelizaveta
AU  - Torosyan Y
AD  - Department of Anatomy, Physiology and Genetics, Institute for Molecular Medicine, 
      Uniformed Services University of Health Sciences School of Medicine, Bethesda, MD 
      20814, USA.
FAU - Simakova, Olga
AU  - Simakova O
FAU - Naga, Shanmugam
AU  - Naga S
FAU - Mezhevaya, Katerina
AU  - Mezhevaya K
FAU - Leighton, Ximena
AU  - Leighton X
FAU - Diaz, Juan
AU  - Diaz J
FAU - Huang, Wei
AU  - Huang W
FAU - Pollard, Harvey
AU  - Pollard H
FAU - Srivastava, Meera
AU  - Srivastava M
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (AR protein, human)
RN  - 0 (Annexin A7)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Annexin A7/*pharmacology
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Blotting, Western
MH  - Cell Cycle/drug effects
MH  - Cell Proliferation/drug effects
MH  - DNA, Neoplasm/genetics
MH  - *Drug Resistance, Neoplasm
MH  - Epithelial Cells/drug effects/metabolism
MH  - Gene Expression Profiling
MH  - Genetic Vectors
MH  - Humans
MH  - Male
MH  - Neoplasms, Hormone-Dependent/genetics/metabolism/*pathology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphorylation
MH  - Prostate/*drug effects/metabolism
MH  - Prostatic Neoplasms/genetics/metabolism/*pathology
MH  - Receptors, Androgen/metabolism
MH  - Retinoblastoma Protein/*metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Proteins/*pharmacology
EDAT- 2009/07/18 09:00
MHDA- 2009/11/07 06:00
CRDT- 2009/07/18 09:00
PHST- 2009/07/18 09:00 [entrez]
PHST- 2009/07/18 09:00 [pubmed]
PHST- 2009/11/07 06:00 [medline]
AID - 10.1002/ijc.24592 [doi]
PST - ppublish
SO  - Int J Cancer. 2009 Dec 1;125(11):2528-39. doi: 10.1002/ijc.24592.