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Studies of human endogenous retroviruses and of the TGF-beta signaling pathway

Kjellman, Christian LU (1999)
Abstract
The human genome, in common with all mammalian genomes, carries a high load of inheritable retroviral sequences. We have identified and characterized a novel family of these endogenous retroviruses and have named this family HERV-F as based on the primer binding sites of three members. The HERV-Fs are C-type endogenous retroviruses that have unique gag, pol and env regions that are, based on phylogenetic analyses, most closely related to the HERV-Hs. Southern blot analysis demonstrates that the HERV-Fs have at least 16 members in the human genome and that related elements exist not only in all Old World monkeys investigated but also in a New World monkey; this indicates an incorporation into the primate lineage some 50-60 million years... (More)
The human genome, in common with all mammalian genomes, carries a high load of inheritable retroviral sequences. We have identified and characterized a novel family of these endogenous retroviruses and have named this family HERV-F as based on the primer binding sites of three members. The HERV-Fs are C-type endogenous retroviruses that have unique gag, pol and env regions that are, based on phylogenetic analyses, most closely related to the HERV-Hs. Southern blot analysis demonstrates that the HERV-Fs have at least 16 members in the human genome and that related elements exist not only in all Old World monkeys investigated but also in a New World monkey; this indicates an incorporation into the primate lineage some 50-60 million years ago. One member, designated HERV-F(XA34), is actively transcribed in human placental and fetal tissue. This element has a complex splicing pattern and the capacity to encode Gag protein. We have also investigated three other families of endogenous retroviruses, HERV-R, HERV-E and RRHERV-I and found in two families, indications of an over-representation of these elements on the Y-chromosome. Human gliomas are known to express high levels of TGF-b and consequently they seem to be resistant to the growth inhibitory effect of exogenous TGF-b. Using tumor material derived from glioma patients, we have investigated the mRNA expression of the TGF-b isoforms and components of the TGF-b signaling pathway. High-grade gliomas were found to express increased levels of TGF-b1, -2 and -3, as well as increased levels of TbRI and -II but decreased levels of Smads. We have also used high-density filter array technology to analyze the effects that the three isoforms of TGF-b have on gene transcription from monocytic cell lines and have found clear and differential effects between the three isoforms. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof Larsson, Erik, Inst. Genetik och Patologi, Uppsala Universitet
organization
publishing date
type
Thesis
publication status
published
subject
keywords
high-density filter array, gliom, TGF-beta, XA34, Human endogenous retrovirus, HERV-F, transplantation, serologi, Immunologi, serology, Immunology
pages
68 pages
publisher
Sölveg. 21, 223 62 Lund, Sweden
defense location
GK-salen, BMC
defense date
1999-10-25 10:15:00
external identifiers
  • other:ISRN: LUMEDW/MECM--99/1035--SE
language
English
LU publication?
yes
id
7297a70e-d72c-4ec5-95a3-28849d9b5c3e (old id 40014)
date added to LUP
2016-04-04 10:06:49
date last changed
2018-11-21 20:56:50
@phdthesis{7297a70e-d72c-4ec5-95a3-28849d9b5c3e,
  abstract     = {{The human genome, in common with all mammalian genomes, carries a high load of inheritable retroviral sequences. We have identified and characterized a novel family of these endogenous retroviruses and have named this family HERV-F as based on the primer binding sites of three members. The HERV-Fs are C-type endogenous retroviruses that have unique gag, pol and env regions that are, based on phylogenetic analyses, most closely related to the HERV-Hs. Southern blot analysis demonstrates that the HERV-Fs have at least 16 members in the human genome and that related elements exist not only in all Old World monkeys investigated but also in a New World monkey; this indicates an incorporation into the primate lineage some 50-60 million years ago. One member, designated HERV-F(XA34), is actively transcribed in human placental and fetal tissue. This element has a complex splicing pattern and the capacity to encode Gag protein. We have also investigated three other families of endogenous retroviruses, HERV-R, HERV-E and RRHERV-I and found in two families, indications of an over-representation of these elements on the Y-chromosome. Human gliomas are known to express high levels of TGF-b and consequently they seem to be resistant to the growth inhibitory effect of exogenous TGF-b. Using tumor material derived from glioma patients, we have investigated the mRNA expression of the TGF-b isoforms and components of the TGF-b signaling pathway. High-grade gliomas were found to express increased levels of TGF-b1, -2 and -3, as well as increased levels of TbRI and -II but decreased levels of Smads. We have also used high-density filter array technology to analyze the effects that the three isoforms of TGF-b have on gene transcription from monocytic cell lines and have found clear and differential effects between the three isoforms.}},
  author       = {{Kjellman, Christian}},
  keywords     = {{high-density filter array; gliom; TGF-beta; XA34; Human endogenous retrovirus; HERV-F; transplantation; serologi; Immunologi; serology; Immunology}},
  language     = {{eng}},
  publisher    = {{Sölveg. 21, 223 62 Lund, Sweden}},
  school       = {{Lund University}},
  title        = {{Studies of human endogenous retroviruses and of the TGF-beta signaling pathway}},
  year         = {{1999}},
}