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c-Jun Contributes to Transcriptional Control of GNA12 Expression in Prostate Cancer Cells.

Publication ,  Journal Article
Udayappan, UK; Casey, PJ
Published in: Molecules
April 10, 2017

Abstract: GNA12 is the α subunit of a heterotrimeric G protein that possesses oncogenic potential. Activated GNA12 also promotes prostate and breast cancer cell invasion in vitro and in vivo, and its expression is up-regulated in many tumors, particularly metastatic tissues. In this study, we explored the control of expression of GNA12 in prostate cancer cells. Initial studies on LnCAP (low metastatic potential, containing low levels of GNA12) and PC3 (high metastatic potential, containing high GNA12 levels) cells revealed that GNA12 mRNA levels correlated with protein levels, suggesting control at the transcriptional level. To identify potential factors controlling GNA12 transcription, we cloned the upstream 5' regulatory region of the human GNA12 gene and examined its activity using reporter assays. Deletion analysis revealed the highest level of promoter activity in a 784 bp region, and subsequent in silico analysis indicated the presence of transcription factor binding sites for C/EBP (CCAAT/enhancer binding protein), CREB1 (cAMP-response-element-binding protein 1), and c-Jun in this minimal element for transcriptional control. A small interfering RNA (siRNA) knockdown approach revealed that silencing of c-Jun expression significantly reduced GNA12 5' regulatory region reporter activity. In addition, chromatin immunoprecipitation assays confirmed that c-Jun binds to the GNA12 5' regulatory region in PC3 cells. Silencing of c-Jun expression reduced mRNA and protein levels of GNA12, but not the closely-related GNA13, in prostate cancer cells. Understanding the mechanisms by which GNA12 expression is controlled may aid in the development of therapies that target key elements responsible for GNA12-mediated tumor progression.

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Published In

Molecules

DOI

EISSN

1420-3049

Publication Date

April 10, 2017

Volume

22

Issue

4

Location

Switzerland

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • RNA, Messenger
  • Proto-Oncogene Proteins c-jun
  • Protein Binding
  • Prostatic Neoplasms
  • Promoter Regions, Genetic
  • Organic Chemistry
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Udayappan, U. K., & Casey, P. J. (2017). c-Jun Contributes to Transcriptional Control of GNA12 Expression in Prostate Cancer Cells. Molecules, 22(4). https://doi.org/10.3390/molecules22040612
Udayappan, Udhaya Kumari, and Patrick J. Casey. “c-Jun Contributes to Transcriptional Control of GNA12 Expression in Prostate Cancer Cells.Molecules 22, no. 4 (April 10, 2017). https://doi.org/10.3390/molecules22040612.
Udayappan, Udhaya Kumari, and Patrick J. Casey. “c-Jun Contributes to Transcriptional Control of GNA12 Expression in Prostate Cancer Cells.Molecules, vol. 22, no. 4, Apr. 2017. Pubmed, doi:10.3390/molecules22040612.

Published In

Molecules

DOI

EISSN

1420-3049

Publication Date

April 10, 2017

Volume

22

Issue

4

Location

Switzerland

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • RNA, Messenger
  • Proto-Oncogene Proteins c-jun
  • Protein Binding
  • Prostatic Neoplasms
  • Promoter Regions, Genetic
  • Organic Chemistry
  • Male
  • Humans