Novel transcripts from a distinct promoter that encode the full-length AKT1 in human breast cancer cells

BMC Cancer

Kay-Uwe Wagner¹  William W West¹  Aleata A Triplett²  Kazuhito Sakamoto²  Barbara L Wehde²  Jeffrey W Schmidt² 

[1]Department of Pathology and Microbiology, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, U.S.A

[2]Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, U.S.A

关键词: Gene expression mRNA;    Proto-oncogene protein c-akt;    Mammary cancer;    Breast cancer;    Transgenic;    Mice;    Human;   

Others  :  858961
DOI  :  10.1186/1471-2407-14-195

 received in 2013-11-11, accepted in 2014-03-07,  发布年份 2014

【 摘 要 】

Background

The serine-threonine kinase AKT1 plays essential roles during normal mammary gland development as well as the initiation and progression of breast cancer. AKT1 is generally considered a ubiquitously expressed gene, and its persistent activation is transcriptionally controlled by regulatory elements characteristic of housekeeping gene promoters. We recently identified a novel Akt1 transcript in mice (Akt1m), which is induced by growth factors and their signal transducers of transcription from a previously unknown promoter. The purpose of this study was to examine whether normal and neoplastic human breast epithelial cells express an orthologous AKT1m transcript and whether its expression is deregulated in cancer cells.

Methods

Initial sequence analyses were performed using the UCSC Genome Browser and GenBank to assess the potential occurrence of an AKT1m transcript variant in human cells and to identify conserved promoter sequences that are orthologous to the murine Akt1m. Quantitative RT-PCR was used to determine the transcriptional activation of AKT1m in mouse mammary tumors as well as 41 normal and neoplastic human breast epithelial cell lines and selected primary breast cancers.

Results

We identified four new AKT1 transcript variants in human breast cancer cells that are orthologous to the murine Akt1m and that encode the full-length kinase. These transcripts originate from an alternative promoter that is conserved between humans and mice. Akt1m is upregulated in the majority of luminal-type and basal-type mammary cancers in four different genetically engineered mouse models. Similarly, a subset of human breast cancer cell lines and primary breast cancers exhibited a higher expression of orthologous AKT1m transcripts.

Conclusions

The existence of an alternative promoter that drives the expression of the unique AKT1m transcript may provide a mechanism by which the levels of AKT1 can be temporally and spatially regulated at particular physiological states, such as cancer, where a heightened activity of this kinase is required.

【 授权许可】

   
2014 Schmidt et al.; licensee BioMed Central Ltd.

【 图 表 】

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