Abstract
To determine how different epithelial cell types respond to the same oncogenic stimulation, we have used a modified human keratin 18 gene to conditionally express the polyomavirus middle T antigen (PyMT) oncogene in simple epithelial tissues of transgenic mice. Activation of PyMT expression by transgenic Cre recombinase in mammary epithelial cells resulted hi carcinomas in all bitransgenic females. PyMT expression induced by K18-driven Cre in internal epithelial organs resulted in pancreatic acinar metaplasia and ductal dysplasia with remarkable desmoplastic stromal responses in all 25 bitransgenic mice. Hepatoma formation with altered lipid metabolism and gastric adenocarcinoma occurred in 96 and 54% of these mice, respectively. Elevated PyMT RNA expression also correlated with intraepithelial neoplasia in the prostate. Activated Erk2 was found in mammary tumors, pancreatic tissues, and affected livers. Hes1 RNA, a target of Notch signaling that has been implicated downstream of Ras pathway activation, was elevated in pancreatic and liver lesions. The variety of responses of different epithelia to PyMT demonstrates the importance of the differentiated state in interpreting oncogenic signals.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 310-320 |
| Number of pages | 11 |
| Journal | American Journal of Pathology |
| Volume | 168 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2006 |
Fingerprint
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Differential sensitivity of mouse epithelial tissues to the polyomavirus middle T oncogene. / Cecena, Grace; Wen, Fang; Cardiff, Robert; Oshima, Robert G.
In: American Journal of Pathology, Vol. 168, No. 1, 01.01.2006, p. 310-320.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential sensitivity of mouse epithelial tissues to the polyomavirus middle T oncogene
AU - Cecena, Grace
AU - Wen, Fang
AU - Cardiff, Robert
AU - Oshima, Robert G.
PY - 2006/1/1
Y1 - 2006/1/1
N2 - To determine how different epithelial cell types respond to the same oncogenic stimulation, we have used a modified human keratin 18 gene to conditionally express the polyomavirus middle T antigen (PyMT) oncogene in simple epithelial tissues of transgenic mice. Activation of PyMT expression by transgenic Cre recombinase in mammary epithelial cells resulted hi carcinomas in all bitransgenic females. PyMT expression induced by K18-driven Cre in internal epithelial organs resulted in pancreatic acinar metaplasia and ductal dysplasia with remarkable desmoplastic stromal responses in all 25 bitransgenic mice. Hepatoma formation with altered lipid metabolism and gastric adenocarcinoma occurred in 96 and 54% of these mice, respectively. Elevated PyMT RNA expression also correlated with intraepithelial neoplasia in the prostate. Activated Erk2 was found in mammary tumors, pancreatic tissues, and affected livers. Hes1 RNA, a target of Notch signaling that has been implicated downstream of Ras pathway activation, was elevated in pancreatic and liver lesions. The variety of responses of different epithelia to PyMT demonstrates the importance of the differentiated state in interpreting oncogenic signals.
AB - To determine how different epithelial cell types respond to the same oncogenic stimulation, we have used a modified human keratin 18 gene to conditionally express the polyomavirus middle T antigen (PyMT) oncogene in simple epithelial tissues of transgenic mice. Activation of PyMT expression by transgenic Cre recombinase in mammary epithelial cells resulted hi carcinomas in all bitransgenic females. PyMT expression induced by K18-driven Cre in internal epithelial organs resulted in pancreatic acinar metaplasia and ductal dysplasia with remarkable desmoplastic stromal responses in all 25 bitransgenic mice. Hepatoma formation with altered lipid metabolism and gastric adenocarcinoma occurred in 96 and 54% of these mice, respectively. Elevated PyMT RNA expression also correlated with intraepithelial neoplasia in the prostate. Activated Erk2 was found in mammary tumors, pancreatic tissues, and affected livers. Hes1 RNA, a target of Notch signaling that has been implicated downstream of Ras pathway activation, was elevated in pancreatic and liver lesions. The variety of responses of different epithelia to PyMT demonstrates the importance of the differentiated state in interpreting oncogenic signals.
UR - http://www.scopus.com/inward/record.url?scp=30344432929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30344432929&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2006.050443
DO - 10.2353/ajpath.2006.050443
M3 - Article
C2 - 16400032
AN - SCOPUS:30344432929
VL - 168
SP - 310
EP - 320
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 1
ER -