A novel transgenic mouse model reveals humanlike regulation of an 8-kbp human TERT gene promoter fragment in normal and tumor tissues.
Standard
A novel transgenic mouse model reveals humanlike regulation of an 8-kbp human TERT gene promoter fragment in normal and tumor tissues. / Ritz, Julia M; Kühle, Olaf; Riethdorf, Sabine; Sipos, Bence; Deppert, Wolfgang; Englert, Christoph; Günes, Cagatay.
in: CANCER RES, Jahrgang 65, Nr. 4, 4, 2005, S. 1187-1196.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - A novel transgenic mouse model reveals humanlike regulation of an 8-kbp human TERT gene promoter fragment in normal and tumor tissues.
AU - Ritz, Julia M
AU - Kühle, Olaf
AU - Riethdorf, Sabine
AU - Sipos, Bence
AU - Deppert, Wolfgang
AU - Englert, Christoph
AU - Günes, Cagatay
PY - 2005
Y1 - 2005
N2 - Telomerase activity is repressed in most human somatic tissues during differentiation processes but strongly up-regulated in most human tumors. Regulation of human telomerase activity primarily occurs at the level of transcriptional initiation of the TERT gene, which encodes the catalytic subunit of telomerase. We have generated a novel transgenic mouse model to study the regulation of the human TERT gene promoter in an in vivo system. For this purpose, we have cloned an 8.0-kbp human TERT promoter fragment in front of the bacterial lacZ reporter gene (hTERTp-lacZ), which encodes the beta-galactosidase enzyme. Expression of the reporter gene was monitored by reverse transcription-PCR analysis, 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining of whole mount preparations, and histologic sections. We find that the activity of the human TERT promoter in most normal mouse tissues recapitulates the expression of the hTERT gene in normal human tissues and is under tighter control when compared with the endogenous mouse TERT gene expression. In testis, where highest lacZ expression was observed, the expression of the reporter gene was restricted to the spermatogonial stem cells and the spermatocytes. Intriguingly, we find increased levels of lacZ expression in mammary tumors of hTERTp-lacZ x p53(+/-) bitransgenic mouse mammary tumor model. Thus, this transgenic mouse model provides a suitable in vivo system to analyze the expression of the human TERT gene under physiologic conditions and during tumorigenesis.
AB - Telomerase activity is repressed in most human somatic tissues during differentiation processes but strongly up-regulated in most human tumors. Regulation of human telomerase activity primarily occurs at the level of transcriptional initiation of the TERT gene, which encodes the catalytic subunit of telomerase. We have generated a novel transgenic mouse model to study the regulation of the human TERT gene promoter in an in vivo system. For this purpose, we have cloned an 8.0-kbp human TERT promoter fragment in front of the bacterial lacZ reporter gene (hTERTp-lacZ), which encodes the beta-galactosidase enzyme. Expression of the reporter gene was monitored by reverse transcription-PCR analysis, 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining of whole mount preparations, and histologic sections. We find that the activity of the human TERT promoter in most normal mouse tissues recapitulates the expression of the hTERT gene in normal human tissues and is under tighter control when compared with the endogenous mouse TERT gene expression. In testis, where highest lacZ expression was observed, the expression of the reporter gene was restricted to the spermatogonial stem cells and the spermatocytes. Intriguingly, we find increased levels of lacZ expression in mammary tumors of hTERTp-lacZ x p53(+/-) bitransgenic mouse mammary tumor model. Thus, this transgenic mouse model provides a suitable in vivo system to analyze the expression of the human TERT gene under physiologic conditions and during tumorigenesis.
KW - Animals
KW - Humans
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Up-Regulation
KW - DNA-Binding Proteins
KW - Models, Animal
KW - Promoter Regions, Genetic
KW - Mice, Transgenic
KW - RNA, Messenger/biosynthesis/genetics
KW - Gene Expression Regulation/genetics
KW - Genes, Reporter/genetics
KW - Genes, p53/genetics
KW - Lac Operon/genetics
KW - Mammary Neoplasms, Experimental/genetics/metabolism
KW - Telomerase/biosynthesis/genetics
KW - Testis/physiology
KW - Animals
KW - Humans
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Up-Regulation
KW - DNA-Binding Proteins
KW - Models, Animal
KW - Promoter Regions, Genetic
KW - Mice, Transgenic
KW - RNA, Messenger/biosynthesis/genetics
KW - Gene Expression Regulation/genetics
KW - Genes, Reporter/genetics
KW - Genes, p53/genetics
KW - Lac Operon/genetics
KW - Mammary Neoplasms, Experimental/genetics/metabolism
KW - Telomerase/biosynthesis/genetics
KW - Testis/physiology
M3 - SCORING: Journal article
VL - 65
SP - 1187
EP - 1196
JO - CANCER RES
JF - CANCER RES
SN - 0008-5472
IS - 4
M1 - 4
ER -
