Production of transgenic mice expressing the Ki-ras oncogene under the control of a thyroglobulin promoter.
Transgenic mice have been generated bearing three fusion genes consisting of: (a) a 900-base pair rat thyroglobulin promoter followed by a gene coding for a chloramphenicol acetyl transferase activity; (b) the same promoter followed by the complementary DNA of the human activated Ki-ras oncogene; (c) a 2000-base pair rat thyroglobulin promoter followed by the complementary DNA of the human activated Ki-ras. We have shown that the 900-base pair rat thyroglobulin promoter is able to direct the expression of the reporter gene specifically in the thyroid gland of transgenic mice. The mice bearing the two Ki-ras constructs, which express the transgene in thyroid glands, show thyroid abnormalities, although at very low incidence. These lesions appear after a long latency and with a benign aspect, thus suggest that, in agreement with literature data on naturally occurring human thyroid tumors, the action of an activated ras gene is not sufficient to attain a complete malignant conversion of thyroid glands in vivo. However, ras expression in thyroid follicular cells represents a favorable ground for tumor development, as shown by the fact that goitrogen stimulation experiments increase the occurrence of tumors.
Santelli
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Servizio di Oncologia Sperimentale E, Istituto per lo Studio e la Cura dei dei Tumori Fondazione G. Pascale, Napoli, Italy.
de Franciscis
V
V
Portella
G
G
Chiappetta
G
G
D'Alessio
A
A
Califano
D
D
Rosati
R
R
Mineo
A
A
Monaco
C
C
Manzo
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G
D000236:Adenoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D008969:Molecular Sequence Data; D010472:Perchlorates / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017670:Sodium Compounds / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D010472:Perchlorates; D012333:RNA, Messenger; D017670:Sodium Compounds; C031068:sodium perchlorate; D015500:Chloramphenicol O-Acetyltransferase; D000640:Amitrole