Transcriptional regulation by targeted expression of architectural transcription factor high mobility group A2 in salivary glands of transgenic mice.
High mobility group A2 (HMGA2) protein is a non-histone architectural transcription factor. Numerous studies have demonstrated that HMGA2 is exclusively expressed in the nucleus of embryonic, but not of terminally differentiated, cells, and aberrant expression of HMGA2 is associated with various benign tumors, including pleomorphic salivary adenoma. Herein, we report the use of a 4.5-kb enhancer/promoter region of the aquaporin-5 (AQP-5) gene to target HMGA2 transgene expression in the mouse salivary acinar cells as a model to investigate the biochemical and biological role of ectopic HMGA2 expression. The expression pattern was analyzed by microarray analyses to profile HMGA2-dependent salivary gene regulation. By using quantitative reverse transcription-polymerase chain reaction (RT-PCR) assays, the expression of a cluster of genes involved in cytokine signaling, including Il7r, Il2rg, and Ptprc, was verified to be up-regulated in the salivary glands of AQP-5/HMGA2 mice. In concert, the expression of a cluster of genes, namely Ppara, Phyh, and Cidea, governing fatty acid and lipid metabolism, was confirmed to be down-regulated by HMGA2. Additionally, squamous carcinoma-like salivary tumors were observed in the AQP-5/HMGA2 transgenic mice, albeit at a low incidence. Our findings indicate that the AQP-5 promoter/enhancer-containing region is sufficient to target salivary-specific transgene expression and suggest novel roles for HMGA2 in salivary epithelial cells.
Lin
H Helen
HH
Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA, USA.
Xiong
Ye
Y
Ho
Ye-Shih
YS
Zhou
Beiyun
B
Nguyen
Ha-Van
HV
Deng
Hongtao
H
Lee
Renee
R
Yen
Yun
Y
Borok
Zea
Z
Ann
David K
DK
D000818:Animals; D051402:Aquaporin 5 / Q000235:genetics* / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D025743:HMGA2 Protein / Q000235:genetics* / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics; D012469:Salivary Glands / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D025743:HMGA2 Protein