PMID- 10519411
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20161124
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 19
DP  - 1999 Oct 1
TI  - Expression of OVCA1, a candidate tumor suppressor, is reduced in tumors and
      inhibits growth of ovarian cancer cells.
PG  - 4973-83
AB  - Loss of all or part of one copy of chromosome 17p is very common in ovarian and
      breast tumors. OVCA1 is a candidate tumor suppressor gene mapping to a highly
      conserved region on chromosome 17p13.3 that shows frequent loss of heterozygosity
      in breast and ovarian carcinomas. Western blot analysis of extracts prepared from
      breast and ovarian carcinomas revealed reduced expression of OVCA1 compared with 
      extracts from normal epithelial cells from these tissues. Subcellular
      localization studies indicate that OVCA1 is localized to punctate bodies
      scattered throughout the cell but is primarily clustered around the nucleus.
      Attempts to create cell lines that stably expressed OVCA1 from the
      cytomegalovirus promoter were generally unsuccessful in a variety of different
      cell lines. This reduction of colony formation was quantified in the ovarian
      cancer cell line A2780, where it was demonstrated that cells transfected with
      plasmids expressing OVCA1 had a 50-60% reduction in colony number as compared
      with appropriate controls, and only a few of these clones expressed OVCA1, albeit
      at low levels. The clones that expressed exogenous OVCA1 were found to have
      dramatically reduced rates of proliferation. Reduced growth rates correlated with
      an increased proportion of the cells in the G1 fraction of the cell cycle
      compared with the parental cell line and decreased levels of cyclin D1. The low
      levels of cyclin D1 appeared to be caused by an accelerated rate of cyclin D1
      degradation. Overexpression of cyclin D1 was able to override OVCA1's suppression
      of clonal outgrowth. These results suggest that slight alterations in the level
      of OVCA1, such as would occur after reduction of chromosome 17p13.13 to
      hemizygosity, may result in cell cycle deregulation and promote tumorigenesis.
FAU - Bruening, W
AU  - Bruening W
AD  - Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia,
      Pennsylvania 19111, USA.
FAU - Prowse, A H
AU  - Prowse AH
FAU - Schultz, D C
AU  - Schultz DC
FAU - Holgado-Madruga, M
AU  - Holgado-Madruga M
FAU - Wong, A
AU  - Wong A
FAU - Godwin, A K
AU  - Godwin AK
LA  - eng
GR  - R01 CA70328/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DPH1 protein, human)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Amino Acid Substitution
MH  - Cell Cycle/genetics
MH  - Cell Division
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 17
MH  - Female
MH  - *Genes, Tumor Suppressor
MH  - *Genetic Variation
MH  - Humans
MH  - Kinetics
MH  - *Loss of Heterozygosity
MH  - Minor Histocompatibility Antigens
MH  - Ovarian Neoplasms/*genetics/*pathology
MH  - Plasmids
MH  - Point Mutation
MH  - Polymorphism, Single-Stranded Conformational
MH  - Proteins/chemistry/*genetics
MH  - Recombinant Proteins/biosynthesis/chemistry
MH  - Tumor Cells, Cultured
MH  - *Tumor Suppressor Proteins
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Oct 1;59(19):4973-83.