PMID- 19251084
OWN - NLM
STAT- MEDLINE
DCOM- 20090325
LR  - 20220316
IS  - 1879-355X (Electronic)
IS  - 0360-3016 (Linking)
VI  - 73
IP  - 4
DP  - 2009 Mar 15
TI  - Major vault protein may affect nonhomologous end-joining repair and apoptosis 
      through Ku70/80 and bax downregulation in cervical carcinoma tumors.
PG  - 976-9
LID - 10.1016/j.ijrobp.2008.11.013 [doi]
AB  - PURPOSE: We investigated the relationship between major vault protein (MVP) 
      expression, the nonhomologous end-joining (NHEJ) repair gene Ku70/80, and related 
      genes involved in the regulation of apoptosis and proliferation to shed light on 
      the possible causes of genetic instability, tumor progression, and resistance to 
      oncologic treatment in patients with clinical cervical cancer. METHODS AND 
      MATERIALS: One hundred sixteen consecutive patients with localized cervix 
      carcinoma were prospectively included in this study from July 1997 to Dec 2003. 
      Patients were staged according to the tumor, node, metastasis (TNM) 
      classification. Forty patients had Stage I disease, 45 had Stage II, and 31 had 
      Stage III/IVA. Most patients had squamous tumors (98 cases) and Grades II (52 
      cases) and III (45 cases) carcinomas. Expression of MVP, Ku70/80, Insulin-Like 
      Growth Factor-1 receptor (IGF-1R), BCL2-associated X protein (BAX), B-cell 
      CLL/lymphoma 2 (BCL-2), p53, and Ki67 was studied by using immunohistochemistry 
      in paraffin-embedded tumor tissue. RESULTS: Tumors overexpressing MVP (65 of 116 
      cases) showed low levels of Ku70/80 (p = 0.013) and BAX expression (p < 0.0001). 
      Furthermore, low Ku70/80 expression was strongly related to suppressed BAX (p < 
      0.001) and, to a lesser extent, upregulated BCL-2 (p = 0.042), altered p53 (p = 
      0.038), and increased proliferation (p = 0.002). CONCLUSION: We hypothesize that 
      an early regulatory mechanism favors homologous or NHEJ repair at first, mediated 
      by vaults along with other factors yet to be elucidated. If vaults are 
      overexpressed, NHEJ repair may be suppressed by means of several mechanisms, with 
      resultant genomic instability. These mechanisms may be associated with the 
      decision of damaged cells to survive and proliferate, favoring tumor progression 
      and reducing tumor response to oncologic treatment through the development of 
      resistant cell phenotypes. Additional clinical studies are necessary to test this 
      hypothesis.
FAU - Lloret, Marta
AU  - Lloret M
AD  - Radiation Oncology Department, Hospital Universitario Dr. Negrin, Las Palmas de 
      Gran Canaria, Spain. mllosae@hotmail.com
FAU - Lara, Pedro Carlos
AU  - Lara PC
FAU - Bordon, Elisa
AU  - Bordon E
FAU - Fontes, Fausto
AU  - Fontes F
FAU - Rey, Agustin
AU  - Rey A
FAU - Pinar, Beatriz
AU  - Pinar B
FAU - Falcon, Orlando
AU  - Falcon O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Radiat Oncol Biol Phys
JT  - International journal of radiation oncology, biology, physics
JID - 7603616
RN  - 0 (Antigens, Nuclear)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Vault Ribonucleoprotein Particles)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (major vault protein)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 3.6.4.12 (Xrcc6 protein, human)
RN  - EC 4.2.99.- (Ku Autoantigen)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigens, Nuclear/genetics/*metabolism
MH  - Apoptosis/*physiology
MH  - Cell Proliferation
MH  - Chromosomal Instability/genetics
MH  - DNA Damage/genetics
MH  - *DNA Repair
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - Ku Autoantigen
MH  - Middle Aged
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Neoplasm Staging
MH  - Prospective Studies
MH  - Receptor, IGF Type 1/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - *Uterine Cervical Neoplasms/genetics/metabolism/pathology/physiopathology
MH  - Vault Ribonucleoprotein Particles/*metabolism
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2009/03/03 09:00
MHDA- 2009/03/26 09:00
CRDT- 2009/03/03 09:00
PHST- 2008/11/16 00:00 [received]
PHST- 2008/11/16 00:00 [revised]
PHST- 2008/11/18 00:00 [accepted]
PHST- 2009/03/03 09:00 [entrez]
PHST- 2009/03/03 09:00 [pubmed]
PHST- 2009/03/26 09:00 [medline]
AID - S0360-3016(08)03791-7 [pii]
AID - 10.1016/j.ijrobp.2008.11.013 [doi]
PST - ppublish
SO  - Int J Radiat Oncol Biol Phys. 2009 Mar 15;73(4):976-9. doi: 
      10.1016/j.ijrobp.2008.11.013.