Transgenic mice demonstrate novel promoter regions for tissue-specific expression of the urokinase receptor gene

Heng Wang, John Hicks, Parham Khanbolooki, Sun Jin Kim, Chunhong Yan, Yao Wang, Douglas Boyd

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The urokinase-type plasminogen activator receptor (u-PAR) contributes to cell migration and proteolysis in normal and cancerous tissues. Currently, there are no reports on the regulatory regions directing tissue-specific expression. Consequently, we undertook a study to identify novel promoter regions required for expression of this gene in transgenic mice bearing a LacZ reporter regulated by varying amounts (0.4, 1.5, and 8.5 kb) of upstream sequence. The 0.4-kb u-PAR upstream sequence directed weak and strong LacZ expression in the placenta and epididymis, respectively, both of which are tissues that express endogenous u-PAR. Conversely, transgene expression in the apical cells of the colon positive for endogenous u-PAR protein required 1.5 kb of upstream sequence for optimal expression. Furthermore, chromatin accessibility assays coupled with real-time polymerase chain reaction suggested a putative regulatory region spanning -1295/-1192 driving u-PAR expression in colonic cells. Interestingly, placental transgene expression was augmented with the 8.5-kb upstream fragment compared with the shorter 1.5-kb fragment indicating contributing element(s) between -1.5 and -8.5 kb. Thus, while 0.4 kb of upstream sequence directs u-PAR expression in the epididymis, sequences located between -0.4 and -1.5 kb and between -1.5 and -8.5 kb are required for optimal tissue-specific expression in the colon and the placenta, respectively.

Original languageEnglish (US)
Pages (from-to)453-464
Number of pages12
JournalAmerican Journal of Pathology
Volume163
Issue number2
DOIs
StatePublished - Aug 1 2003

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Urokinase Plasminogen Activator Receptors
Urokinase-Type Plasminogen Activator
Genetic Promoter Regions
Transgenic Mice
Genes
Epididymis
Nucleic Acid Regulatory Sequences
Transgenes
Placenta
Colon
Proteolysis
Chromatin
Cell Movement
Real-Time Polymerase Chain Reaction
Gene Expression

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Transgenic mice demonstrate novel promoter regions for tissue-specific expression of the urokinase receptor gene. / Wang, Heng; Hicks, John; Khanbolooki, Parham; Kim, Sun Jin; Yan, Chunhong; Wang, Yao; Boyd, Douglas.

In: American Journal of Pathology, Vol. 163, No. 2, 01.08.2003, p. 453-464.

Research output: Contribution to journalArticle

Wang, Heng ; Hicks, John ; Khanbolooki, Parham ; Kim, Sun Jin ; Yan, Chunhong ; Wang, Yao ; Boyd, Douglas. / Transgenic mice demonstrate novel promoter regions for tissue-specific expression of the urokinase receptor gene. In: American Journal of Pathology. 2003 ; Vol. 163, No. 2. pp. 453-464.
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