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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)
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author
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
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
2007-06-21 11:53:06
date last changed
2016-09-19 08:45:02
@misc{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},
  keyword      = {high-density filter array,gliom,TGF-beta,XA34,Human endogenous retrovirus,HERV-F,transplantation,serologi,Immunologi,serology,Immunology},
  language     = {eng},
  pages        = {68},
  publisher    = {ARRAY(0x90e90f8)},
  title        = {Studies of human endogenous retroviruses and of the TGF-beta signaling pathway},
  year         = {1999},
}