Targeting oncogenesis by introduction of a 5.2-kbp segment of the 5' regulatory region of the human thyrotropin beta-subunit gene.
We produced transgenic mice carrying a fusion gene (TTP-5) consisting of a 5.2-kbp segment of the 5' flanking sequence of the human thyrotropin beta-subunit (TSH beta) gene linked to the simian virus 40 large T antigen (SVT) gene. These mice developed pituitary tumors 6 months after birth and wasted away. With the 5.2-kbp TSH beta 5' flanking region governing SVT expression, SVT mRNA was present in the pituitary and testis but not in other tissues, as detected by the reverse transcriptase-polymerase chain reaction. Histological and immunohistochemical analyses showed that the pituitary tumors of the transgenic mice were composed of moderately differentiated pituitary cells that expressed TSH, growth hormone, and prolactin. These results indicate that the 5.2-kbp segment of the human TSH beta 5' regulatory region is sufficient to drive expression of SVT and induce tumorigenesis of hormone-producing pituitary cells in transgenic mice.
Miyoshi
I
I
Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, Sendai, Japan. ichirom@mail.cc.tohoku.ac.jp
Maki
K
K
Kon
Y
Y
Yamashita
T
T
Aoyama
S
S
Hayashizaki
Y
Y
Kasai
N
N
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000737:chemistry; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011388:Prolactin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid; D013737:Testis / Q000737:chemistry; D013972:Thyrotropin / Q000235:genetics*
D000952:Antigens, Polyomavirus Transforming; D012333:RNA, Messenger; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone