Abstract
DNA replication-initiation proteins are expressed in cancer cells, whereas some of these proteins are not expressed in nonproliferating normal cells. Therefore, replication-initiation proteins may present attractive targets for anticancer therapy. Using selected antisense oligodeoxynucleotides and small interfering RNA molecules targeted to the mRNA encoding the DNA replication-initiation proteins hCdc6p, hMcm2p, and hCdc45p, we show that the target genes could be effectively and specifically silenced and that, consequently, DNA replication and cell proliferation were inhibited in cultured human cells. In addition, silencing of these genes resulted in apoptosis in both p53-positive and -negative cancer cells but not in normal cells: cancer cells entered an abortive S-phase, whereas normal cells arrested mainly in G1 phase. Our studies are the first to suggest that inhibiting the expression of selective replication-initiation proteins is a novel and effective anticancer strategy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7356-7364 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 63 |
| Issue number | 21 |
| State | Published - Nov 1 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Inhibiting the Expression of DNA Replication-Initiation Proteins Induces Apoptosis in Human Cancer Cells. / Feng, Daorong; Tu, Zheng; Wu, Wenyan; Liang, Chun.
In: Cancer Research, Vol. 63, No. 21, 01.11.2003, p. 7356-7364.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibiting the Expression of DNA Replication-Initiation Proteins Induces Apoptosis in Human Cancer Cells
AU - Feng, Daorong
AU - Tu, Zheng
AU - Wu, Wenyan
AU - Liang, Chun
PY - 2003/11/1
Y1 - 2003/11/1
N2 - DNA replication-initiation proteins are expressed in cancer cells, whereas some of these proteins are not expressed in nonproliferating normal cells. Therefore, replication-initiation proteins may present attractive targets for anticancer therapy. Using selected antisense oligodeoxynucleotides and small interfering RNA molecules targeted to the mRNA encoding the DNA replication-initiation proteins hCdc6p, hMcm2p, and hCdc45p, we show that the target genes could be effectively and specifically silenced and that, consequently, DNA replication and cell proliferation were inhibited in cultured human cells. In addition, silencing of these genes resulted in apoptosis in both p53-positive and -negative cancer cells but not in normal cells: cancer cells entered an abortive S-phase, whereas normal cells arrested mainly in G1 phase. Our studies are the first to suggest that inhibiting the expression of selective replication-initiation proteins is a novel and effective anticancer strategy.
AB - DNA replication-initiation proteins are expressed in cancer cells, whereas some of these proteins are not expressed in nonproliferating normal cells. Therefore, replication-initiation proteins may present attractive targets for anticancer therapy. Using selected antisense oligodeoxynucleotides and small interfering RNA molecules targeted to the mRNA encoding the DNA replication-initiation proteins hCdc6p, hMcm2p, and hCdc45p, we show that the target genes could be effectively and specifically silenced and that, consequently, DNA replication and cell proliferation were inhibited in cultured human cells. In addition, silencing of these genes resulted in apoptosis in both p53-positive and -negative cancer cells but not in normal cells: cancer cells entered an abortive S-phase, whereas normal cells arrested mainly in G1 phase. Our studies are the first to suggest that inhibiting the expression of selective replication-initiation proteins is a novel and effective anticancer strategy.
UR - http://www.scopus.com/inward/record.url?scp=0242610832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242610832&partnerID=8YFLogxK
M3 - Article
C2 - 14612534
AN - SCOPUS:0242610832
VL - 63
SP - 7356
EP - 7364
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 21
ER -