Page 23 - L. Genetics and genomics

ETS transcription factor ELF3 activates
transcriptional activity of Cripto-1 promoter

Wonbin Choi, Sung-Won Park, Hyun-Jin Do, Jae-Hwan Kim
Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do 13488, Republic of Korea
BACKGROUND AIM

Cripto-1, known as teratocarcinoma-derived growth factor 1 (TDGF1), To understand whether EMT-related factors regulate
belongs to a family of epidermal growth factor-related peptides and is tumorigenesis in cancer, we investigated whether the
transcriptional regulation of Cripto-1 is mediated by ELF3 in
involved in the regulation of epithelial-to-mesenchymal transition (EMT) human embryonic carcinoma NCCIT cells. Both Cripto-1 and ELF3
processes during embryonic development. E74-like ETS transcription seem to play important roles in EMT processes and they are
factor 3 (ELF3), a member of ETS transcription factors, plays important overexpressed in various cancer types such as prostate, breast,
roles in invasion, migration, and tumor progression, which are similar to embryonal carcinoma cell. ELF3-mediated regulation of Cripto-1
expression in embryonic cancer cells can be understood in EMT-
the biological processes of EMT. related regulatory mechanisms in tumor development.

RESULTS

Figure 1 Figure 2

Figure 2. Transcription activity of Cripto-1 promoter serial deletion mutants by
ELF3 in NCCIT cells.
Serial deletion mutants of Cripto-1 promoter (-3320-Luc, -2595-Luc, -2104-Luc, -
1718-Luc, -1048-Luc, -500-Luc, -100-Luc) were co-transfected into NCCIT cells
along with ELF3 expression vector. Transcriptional activities were calculated
relative to the expression of pGL3-Basic vector as a negative control. **P<0.01.

Figure 1. Transcriptional activation of Cripto-1 promoter by a Figure 3 Figure 3. Transcriptional activation
dose-dependent ELF3 overexpression in NCCIT cells. of Cripto-1 minimal promoter (-
100~-1) by ELF3 in a dose-
(A) Schematic diagram of Cripto-1 promoter-reporter (-3320- dependent manner.
Luc), ELF3 expression vector : ELF3 functional domains are
indicated as , pointed domain, transactivation domain, serine- (A) Schematic diagram of Cripto-1
and aspartic acid-rich domain, A/T hook domain and the ETS promoter-reporters (-100-Luc) and
(B)
vector.
DNA binding domain (POINTED, TAD, SAR, AT and ETS). (B) ELF3 expression activities were
Transcriptional
Transcriptional activities were calculated relative to the calculated relative to the
expression of pGL3-Basic vector as a negative control. expression of pGL3-Basic vector as
abcde P<0.05. a negative control. abcde P<0.05

CONCLUSION REFERENCES
1. Transcription activity of Cripto-1 full length promoter was increased by a dose- 1. Rangel et al. (2012), Am J Pathol. 2012 Jun; 180(6): 2188–
200
dependent overexpression of ELF3. 2. Cao. (2017), Cell Biosci 7:61
2. A series of deletion mutagenesis found that the upstream region of Cripto-1 minimal 3. Zheng et al. (2018), Cell Death and Disease 9:387
promoter is sufficient to activate basal transcriptional activity. 4. Bianco et al. (2010), Am J Pathol. Aug;177(2):532-40
3. The dose-dependent overexpression of ELF3 significantly increased the Cripto-1 5. Castro et al. (2010), Future Oncol. Jul;6(7):1127-425
minimal promoter
Contact information
This study suggests that ELF3 seems to play an important role in embryonic gene Cripto-1
expression as a transcriptional activator in human embryonal carcinoma NCCIT cells. Corresponding author.
E-mail address: jaehwan_k@cha.ac.kr (J.-H. Kim).