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

Jeffrey W. Schmidt, Barbara L. Wehde, Kazuhito Sakamoto, Aleata A. Triplett, William W. West, Kay Uwe Wagner

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number195
JournalBMC Cancer
Volume14
Issue number1
DOIs
StatePublished - Mar 15 2014

Fingerprint

Breast Neoplasms
Breast
Phosphotransferases
Epithelial Cells
Cell Line
Conserved Sequence
Protein-Serine-Threonine Kinases
Essential Genes
Nucleic Acid Databases
Human Mammary Glands
Transducers
Transcriptional Activation
Sequence Analysis
Neoplasms
Intercellular Signaling Peptides and Proteins
Genome
Polymerase Chain Reaction
Genes

Keywords

  • Breast cancer
  • Gene expression mRNA
  • Human
  • Mammary cancer
  • Mice
  • Proto-oncogene protein c-akt
  • Transgenic

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Schmidt, J. W., Wehde, B. L., Sakamoto, K., Triplett, A. A., West, W. W., & Wagner, K. U. (2014). Novel transcripts from a distinct promoter that encode the full-length AKT1 in human breast cancer cells. BMC Cancer, 14(1), [195]. https://doi.org/10.1186/1471-2407-14-195

Novel transcripts from a distinct promoter that encode the full-length AKT1 in human breast cancer cells. / Schmidt, Jeffrey W.; Wehde, Barbara L.; Sakamoto, Kazuhito; Triplett, Aleata A.; West, William W.; Wagner, Kay Uwe.

In: BMC Cancer, Vol. 14, No. 1, 195, 15.03.2014.

Research output: Contribution to journalArticle

Schmidt, JW, Wehde, BL, Sakamoto, K, Triplett, AA, West, WW & Wagner, KU 2014, 'Novel transcripts from a distinct promoter that encode the full-length AKT1 in human breast cancer cells', BMC Cancer, vol. 14, no. 1, 195. https://doi.org/10.1186/1471-2407-14-195
Schmidt, Jeffrey W. ; Wehde, Barbara L. ; Sakamoto, Kazuhito ; Triplett, Aleata A. ; West, William W. ; Wagner, Kay Uwe. / Novel transcripts from a distinct promoter that encode the full-length AKT1 in human breast cancer cells. In: BMC Cancer. 2014 ; Vol. 14, No. 1.
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abstract = "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.",
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