Abstract
We previously showed that a mammary-specific dominant-negative p53 transgene (WAP-p53172H) could accelerate ErbB2-induced mammary tumorigenesis in mice, but was not tumorigenic on its own. To identify other genes that cooperate with WAP-p53172H in tumorigenesis, we performed mouse mammary tumor virus (MMTV) proviral mutagenesis. We derived F1, N2, and N4/N5 mice from p53172H transgenic FVB mice backcrossed onto MMTV+ C3H/He mice. Results show the latency of MMTV tumorigenesis is correlated with FVB contribution. F1 tumors had the shortest latency (217 days), had a higher rate of metastasis, and were less differentiated than the N2 and N4/N5 tumors. The latency was 269 days in N2 mice, and lengthened to 346 days in N4/N5 mice. p53172H significantly accelerated MMTV tumorigenesis only in N2 mice, indicating cooperativity between p53172H and MMTV in this cohort. To identify genes that may be causally involved in MMTV-induced mammary tumorigenesis, we identified 60 sites of proviral insertion in the N2 tumors. Among the insertions in p53172H transgenic tumors were 10 genes not previously found as sites of MMTV insertion including genes involved in signaling (Pdgfra, Pde1b, Cnk1), cell adhesion (Cd44), angiogenesis (Galgt1), and transcriptional regulation (Olig1, Olig2, and Uncx4.1). These may represent cellular functions that are likely not deregulated by mutation in p53.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2241-2253 |
| Number of pages | 13 |
| Journal | American Journal of Pathology |
| Volume | 161 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1 2002 |
Fingerprint
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Acceleration of mouse mammary tumor virus-induced murine mammary tumorigenesis by a p53172H transgene : Influence of FVB background on tumor latency and identification of novel sites of proviral insertion. / Chatterjee, Gouri; Rosner, Andrea; Han, Yi; Zelazny, Edward T.; Li, Baolin; Cardiff, Robert; Perkins, Archibald S.
In: American Journal of Pathology, Vol. 161, No. 6, 01.12.2002, p. 2241-2253.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acceleration of mouse mammary tumor virus-induced murine mammary tumorigenesis by a p53172H transgene
T2 - Influence of FVB background on tumor latency and identification of novel sites of proviral insertion
AU - Chatterjee, Gouri
AU - Rosner, Andrea
AU - Han, Yi
AU - Zelazny, Edward T.
AU - Li, Baolin
AU - Cardiff, Robert
AU - Perkins, Archibald S.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - We previously showed that a mammary-specific dominant-negative p53 transgene (WAP-p53172H) could accelerate ErbB2-induced mammary tumorigenesis in mice, but was not tumorigenic on its own. To identify other genes that cooperate with WAP-p53172H in tumorigenesis, we performed mouse mammary tumor virus (MMTV) proviral mutagenesis. We derived F1, N2, and N4/N5 mice from p53172H transgenic FVB mice backcrossed onto MMTV+ C3H/He mice. Results show the latency of MMTV tumorigenesis is correlated with FVB contribution. F1 tumors had the shortest latency (217 days), had a higher rate of metastasis, and were less differentiated than the N2 and N4/N5 tumors. The latency was 269 days in N2 mice, and lengthened to 346 days in N4/N5 mice. p53172H significantly accelerated MMTV tumorigenesis only in N2 mice, indicating cooperativity between p53172H and MMTV in this cohort. To identify genes that may be causally involved in MMTV-induced mammary tumorigenesis, we identified 60 sites of proviral insertion in the N2 tumors. Among the insertions in p53172H transgenic tumors were 10 genes not previously found as sites of MMTV insertion including genes involved in signaling (Pdgfra, Pde1b, Cnk1), cell adhesion (Cd44), angiogenesis (Galgt1), and transcriptional regulation (Olig1, Olig2, and Uncx4.1). These may represent cellular functions that are likely not deregulated by mutation in p53.
AB - We previously showed that a mammary-specific dominant-negative p53 transgene (WAP-p53172H) could accelerate ErbB2-induced mammary tumorigenesis in mice, but was not tumorigenic on its own. To identify other genes that cooperate with WAP-p53172H in tumorigenesis, we performed mouse mammary tumor virus (MMTV) proviral mutagenesis. We derived F1, N2, and N4/N5 mice from p53172H transgenic FVB mice backcrossed onto MMTV+ C3H/He mice. Results show the latency of MMTV tumorigenesis is correlated with FVB contribution. F1 tumors had the shortest latency (217 days), had a higher rate of metastasis, and were less differentiated than the N2 and N4/N5 tumors. The latency was 269 days in N2 mice, and lengthened to 346 days in N4/N5 mice. p53172H significantly accelerated MMTV tumorigenesis only in N2 mice, indicating cooperativity between p53172H and MMTV in this cohort. To identify genes that may be causally involved in MMTV-induced mammary tumorigenesis, we identified 60 sites of proviral insertion in the N2 tumors. Among the insertions in p53172H transgenic tumors were 10 genes not previously found as sites of MMTV insertion including genes involved in signaling (Pdgfra, Pde1b, Cnk1), cell adhesion (Cd44), angiogenesis (Galgt1), and transcriptional regulation (Olig1, Olig2, and Uncx4.1). These may represent cellular functions that are likely not deregulated by mutation in p53.
UR - http://www.scopus.com/inward/record.url?scp=0036900928&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036900928&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64500-2
DO - 10.1016/S0002-9440(10)64500-2
M3 - Article
C2 - 12466138
AN - SCOPUS:0036900928
VL - 161
SP - 2241
EP - 2253
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 6
ER -