PMID- 10097138
OWN - NLM
STAT- MEDLINE
DCOM- 19990512
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 7
DP  - 1999 Mar 30
TI  - RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung 
      metastases in Rb+/- mice.
PG  - 3916-21
AB  - Alterations in pathways mediated by retinoblastoma susceptibility gene (RB) 
      product are among the most common in human cancer. Mice with a single copy of the 
      Rb gene are shown to develop a syndrome of multiple neuroendocrine neoplasia. The 
      earliest Rb-deficient atypical cells were identified in the intermediate and 
      anterior lobes of the pituitary, the thyroid and parathyroid glands, and the 
      adrenal medulla within the first 3 months of postnatal development. These cells 
      form gross tumors with various degrees of malignancy by postnatal day 350. By age 
      of 380 days, 84% of Rb+/- mice exhibited lung metastases from C-cell thyroid 
      carcinomas. Expression of a human RB transgene in the Rb+/- mice suppressed 
      carcinogenesis in all tissues studied. Of particular clinical relevance, the 
      frequency of lung metastases also was reduced to 12% in Rb+/- mice by repeated 
      i.v. administration of lipid-entrapped, polycation-condensed RB complementary 
      DNA. Thus, in spite of long latency periods during which secondary alterations 
      can accumulate, the initial loss of Rb function remains essential for tumor 
      progression in multiple types of neuroendocrine cells. Restoration of RB function 
      in humans may prove an effective general approach to the treatment of 
      RB-deficient disseminated tumors.
FAU - Nikitin, A Y
AU  - Nikitin AY
AD  - Department of Molecular Medicine and Institute of Biotechnology, The University 
      of Texas Health Science Center, San Antonio, TX 78245-3207, USA.
FAU - Juarez-Perez, M I
AU  - Juarez-Perez MI
FAU - Li, S
AU  - Li S
FAU - Huang, L
AU  - Huang L
FAU - Lee, W H
AU  - Lee WH
LA  - eng
GR  - CA58318/CA/NCI NIH HHS/United States
GR  - CA71731/CA/NCI NIH HHS/United States
GR  - EY05785/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Animals
MH  - Chimera
MH  - *Genes, Retinoblastoma
MH  - Genetic Therapy
MH  - Humans
MH  - Lung Neoplasms/genetics/pathology/prevention & control/*secondary
MH  - Mice
MH  - Mice, Transgenic
MH  - Multiple Endocrine Neoplasia/*genetics/pathology/*prevention & control
MH  - Polymerase Chain Reaction
MH  - Retinoblastoma Protein/*deficiency/genetics
PMC - PMC22395
EDAT- 1999/03/31 00:00
MHDA- 1999/03/31 00:01
PMCR- 1999/09/30
CRDT- 1999/03/31 00:00
PHST- 1999/03/31 00:00 [pubmed]
PHST- 1999/03/31 00:01 [medline]
PHST- 1999/03/31 00:00 [entrez]
PHST- 1999/09/30 00:00 [pmc-release]
AID - 3363 [pii]
AID - 10.1073/pnas.96.7.3916 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3916-21. doi: 10.1073/pnas.96.7.3916.