PMID- 10208428
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 9
DP  - 1999 Mar 4
TI  - Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase
      inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing
      cell cycle arrest, apoptosis and inhibition of tumorigenicity.
PG  - 1663-76
AB  - Cell cycle regulatory proteins are important candidates for therapeutic tumour
      suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase
      inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the
      control of the murine cytomegalovirus immediate early gene promoter. These
      vectors directed the efficient expression of each of the cyclin kinase inhibitors
      and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation
      of the retinoblastoma protein (pRb) in cell lines expressing functional pRb. In
      pRb-deficient cells, expression of the cyclin kinase inhibitors was not effective
      in inhibiting DNA replication or growth arrest. Interestingly, three of the
      cyclin kinase inhibitors, p16, p18 and p27 were found to induce apoptotic death
      in transduced HeLa and A549 cells. When the vectors were tested for their ability
      to inhibit tumorigenicity in a polyomavirus middle T antigen model of murine
      breast carcinoma, expression of the cyclin kinase inhibitors resulted in a delay 
      in tumour formation that varied from several weeks for the p19 expressing vector 
      to greater than 25 weeks for the p27 expressing vector. When tumours were
      injected directly with the adenovirus vectors expressing the cyclin kinase
      inhibitors, only treatment with the vector expressing p16 resulted in a delay in 
      tumour growth.
FAU - Schreiber, M
AU  - Schreiber M
AD  - Department of Biology, McMaster University, Hamilton, Ontario, Canada.
FAU - Muller, W J
AU  - Muller WJ
FAU - Singh, G
AU  - Singh G
FAU - Graham, F L
AU  - Graham FL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (CDKN1A protein, human)
RN  - 0 (CDKN2C protein, human)
RN  - 0 (CDKN2D protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p19)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Adenocarcinoma
MH  - *Adenoviruses, Human
MH  - Animals
MH  - *Apoptosis
MH  - Blotting, Western
MH  - Carcinogenicity Tests
MH  - Carrier Proteins/*biosynthesis/genetics
MH  - Cell Cycle
MH  - *Cell Cycle Proteins
MH  - Cell Division
MH  - Cell Line, Transformed
MH  - Cyclin-Dependent Kinase Inhibitor p16/*biosynthesis/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p18
MH  - Cyclin-Dependent Kinase Inhibitor p19
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Cyclin-Dependent Kinases/*antagonists & inhibitors
MH  - Cyclins/*biosynthesis/genetics
MH  - *Enzyme Inhibitors
MH  - *Genetic Vectors
MH  - HeLa Cells
MH  - Humans
MH  - Mammary Neoplasms, Experimental
MH  - Microtubule-Associated Proteins/*biosynthesis/genetics
MH  - Phosphorylation
MH  - Retinoblastoma Protein/metabolism
MH  - Transgenes
MH  - *Tumor Suppressor Proteins
EDAT- 1999/04/20 00:00
MHDA- 1999/04/20 00:01
CRDT- 1999/04/20 00:00
PHST- 1999/04/20 00:00 [pubmed]
PHST- 1999/04/20 00:01 [medline]
PHST- 1999/04/20 00:00 [entrez]
AID - 10.1038/sj.onc.1202466 [doi]
PST - ppublish
SO  - Oncogene. 1999 Mar 4;18(9):1663-76. doi: 10.1038/sj.onc.1202466.