Abstract
We have previously generated transgenic mice bearing a molecular construct obtained by fusing the rat thyroglobulin promoter with the human Kirsten ras oncogene (KRAS). These mice showed thyroid abnormalities, although at very low incidence and after a long latency period. A six-month thyrotropin (TSH) stimulation of thyroid glands, followed by a two-month suspension, induced a significant increase in the number of lesions in transgenic mice as compared with a nontransgenic control group. Our goal was to follow the progression and the reversion of the tumorigenesis process in relationship with the levels of expression of the KRAS in this experimental model. In situ hybridization was used to detect expression of KRAS mRNA in sections of thyroids of the various groups of mice. A positive hybridization was observed in follicular cells of TSH-stimulated transgenic mice, whereas no expression could be appreciated in control nontransgenic mice. A positive signal was also observed in thyroid glands excised from transgenic mice after the 2- month suspension of treatment; however, the number of expressing cells was decreased compared with transgenic mice killed immediately after 6 months of a goitrogen regimen. Finally, every cell in the single thyroid carcinoma observed after the two-month suspension was positive for the transgene mRNA. This study further strengthens the role of the expression of mutated KRAS in the early stages of thyroid follicular cell transformation and indicates that when the expression of the mutated KRAS becomes independent of exogenous TSH stimulation, this event coincides with a further progression towards tumorigenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 85-93 |
| Number of pages | 9 |
| Journal | Oncology Research |
| Volume | 8 |
| Issue number | 2 |
| Publication status | Published - 1996 |
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Keywords
- in situ hybridization
- KRAS
- thyroid
- transgenic mice
ASJC Scopus subject areas
- Cancer Research
Cite this
Transgenic mice carrying the human KRAS oncogene under the control of a thyroglobulin promoter : KRAS expression in thyroids analyzed by in situ hybridization. / Chiappetta, Gennaro; Fabien, Nicole; Picone, Alessandro; Califano, Daniela; Monaco, Carmen; De Franciscis, Vittorio; Vecchio, Giancarlo; Santelli, Giovanni.
In: Oncology Research, Vol. 8, No. 2, 1996, p. 85-93.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transgenic mice carrying the human KRAS oncogene under the control of a thyroglobulin promoter
T2 - KRAS expression in thyroids analyzed by in situ hybridization
AU - Chiappetta, Gennaro
AU - Fabien, Nicole
AU - Picone, Alessandro
AU - Califano, Daniela
AU - Monaco, Carmen
AU - De Franciscis, Vittorio
AU - Vecchio, Giancarlo
AU - Santelli, Giovanni
PY - 1996
Y1 - 1996
N2 - We have previously generated transgenic mice bearing a molecular construct obtained by fusing the rat thyroglobulin promoter with the human Kirsten ras oncogene (KRAS). These mice showed thyroid abnormalities, although at very low incidence and after a long latency period. A six-month thyrotropin (TSH) stimulation of thyroid glands, followed by a two-month suspension, induced a significant increase in the number of lesions in transgenic mice as compared with a nontransgenic control group. Our goal was to follow the progression and the reversion of the tumorigenesis process in relationship with the levels of expression of the KRAS in this experimental model. In situ hybridization was used to detect expression of KRAS mRNA in sections of thyroids of the various groups of mice. A positive hybridization was observed in follicular cells of TSH-stimulated transgenic mice, whereas no expression could be appreciated in control nontransgenic mice. A positive signal was also observed in thyroid glands excised from transgenic mice after the 2- month suspension of treatment; however, the number of expressing cells was decreased compared with transgenic mice killed immediately after 6 months of a goitrogen regimen. Finally, every cell in the single thyroid carcinoma observed after the two-month suspension was positive for the transgene mRNA. This study further strengthens the role of the expression of mutated KRAS in the early stages of thyroid follicular cell transformation and indicates that when the expression of the mutated KRAS becomes independent of exogenous TSH stimulation, this event coincides with a further progression towards tumorigenesis.
AB - We have previously generated transgenic mice bearing a molecular construct obtained by fusing the rat thyroglobulin promoter with the human Kirsten ras oncogene (KRAS). These mice showed thyroid abnormalities, although at very low incidence and after a long latency period. A six-month thyrotropin (TSH) stimulation of thyroid glands, followed by a two-month suspension, induced a significant increase in the number of lesions in transgenic mice as compared with a nontransgenic control group. Our goal was to follow the progression and the reversion of the tumorigenesis process in relationship with the levels of expression of the KRAS in this experimental model. In situ hybridization was used to detect expression of KRAS mRNA in sections of thyroids of the various groups of mice. A positive hybridization was observed in follicular cells of TSH-stimulated transgenic mice, whereas no expression could be appreciated in control nontransgenic mice. A positive signal was also observed in thyroid glands excised from transgenic mice after the 2- month suspension of treatment; however, the number of expressing cells was decreased compared with transgenic mice killed immediately after 6 months of a goitrogen regimen. Finally, every cell in the single thyroid carcinoma observed after the two-month suspension was positive for the transgene mRNA. This study further strengthens the role of the expression of mutated KRAS in the early stages of thyroid follicular cell transformation and indicates that when the expression of the mutated KRAS becomes independent of exogenous TSH stimulation, this event coincides with a further progression towards tumorigenesis.
KW - in situ hybridization
KW - KRAS
KW - thyroid
KW - transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=0029927950&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029927950&partnerID=8YFLogxK
M3 - Article
C2 - 8859779
AN - SCOPUS:0029927950
VL - 8
SP - 85
EP - 93
JO - Oncology Research
JF - Oncology Research
SN - 0965-0407
IS - 2
ER -