T cell lymphoma in transgenic mice expressing the human Hsp70 gene.
In the course of studying the role of hsp70 in the differentiation of pancreatic beta cells, transgenic founder mice were generated with the human hsp70 gene fused to the human insulin gene promoter. One resulted in a transgenic line that consistently developed diabetes mellitus, but unexpectedly three other independent transgenic founders developed generalized malignant lymphoma within 10 months after birth. Immunochemical and RT-PCR analyses revealed that the transgene was expressed in the lymphoma cells. Flow cytometric analyses revealed that the tumor was originated from T lymphocytes. Our results provide the first experimental evidence that hsp70 is involved in the tumorigenesis of T cells most likely through the blockage of apoptotic signals.
Seo
J S
JS
Transgenic Mice Center, Cancer Research Institute, Seoul, Korea.
Park
Y M
YM
Kim
J I
JI
Shim
E H
EH
Kim
C W
CW
Jang
J J
JJ
Kim
S H
SH
Lee
W H
WH
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000235:genetics; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment
D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D007328:Insulin; D012333:RNA, Messenger