Korean Journal of Microbiology (미생물학회지)

The Microbiological Society of Korea (한국미생물학회)
권호 표지
DOI QR코드

DOI QR Code

Suppression of metastasis-related ERBB2 and PLAU expressions in human breast cancer MCF 7 cells by fermented soybean extract

발효대두추출물의 인간 유방암 MCF7 세포에서 전이 관련 ERBB2와 PLAU 발현 억제 효과

  • Park, Jameon (Department of Biotechnology, Hoseo University) ;
  • Kim, Han Bok (Department of Biotechnology, Hoseo University)
  • 박잠언 (호서대학교 생명공학과) ;
  • 김한복 (호서대학교 생명공학과)
  • Received : 2018.10.12
  • Accepted : 2018.10.29
  • Published : 2018.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Chunkookjang, fermented soybean is rich in diverse oligopeptides which derived from cleavage of soybean proteins during fermentation. Microarray data containing differently expressed genes in breast cancer cells treated with fermented soybean extract and well known breast cancer metastasis markers were combined, and a new network was constructed. It is used to check interactions between the marker proteins and the differently expressed genes. Based on the network analysis, PLAU (plasminogen activator, urokinase, uPA) and ERBB2 (epidermal growth factor receptor 2) are chosen as possible metastasis genes. We treated breast cancer MCF7 cells with fermented soybean extract and measured expression levels of PLAU and ERBB2. Fermented soybean extract suppressed PLAU and ERBB2 expressions conspicuously. In the cancer cells treated with fermented soybean extracts, an inflammation marker, NO production was also reduced. It will be interesting to find specific peptides to suppress PLAU and ERBB2 expressions in human breast cancer cells.

발효대두 청국장에는 대두단백질이 발효에 의해 분해 형성된 다양한 펩타이드류가 들어 있다. 청국장 추출물이 처리된 유방암세포의 microarray data와 잘 알려진 유방암 전이 마커를 합쳐서 새로운 연결망이 제조되었으며 이를 이용해 전이 마커와 발현 차이가 있는 단백질 사이의 상호작용을 체크하였다. 연결망 분석을 통해 PLAU (plasminogen activator, urokinase, uPA)와 ERBB2 (epidermal growth factor receptor 2)를 실제 전이 가능성을 보여주는 유전자로 선택하였다. MCF7 암세포를 청국장추출물로 처리하고 PLAU와 ERBB2 발현정도를 측정하였다. 청국장 추출물은 PLAU와 ERBB2 발현을 상당히 억제하였다. 청국장 추출물을 처리한 암세포에서 염증 마커인 NO의 생산이 감소하였다. 인간 유방암세포에서 PLAU와 ERBB2 발현을 특이적으로 감소시키는 펩타이드를 찾아내는 것은 흥미로운 일일 것이다.

Keywords

MSMHBQ_2018_v54n4_320_f0001.png 이미지

Fig. 1. Network analysis.

MSMHBQ_2018_v54n4_320_f0002.png 이미지

Fig. 2. Metastasis gene expressions.

MSMHBQ_2018_v54n4_320_f0003.png 이미지

Fig. 3. NO assay.

References

  1. Asuthkar S, Stepanova V, Levedeva T, Holterman AL, Esters N, Cines DB, Rao JS, and Gondi CS. 2013. Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer. Mol. Biol. Cell 24, 2620-2632. https://doi.org/10.1091/mbc.e12-04-0306
  2. Choudhari SK, Chaudhari M, Badge S, Gadbail AR, and Joshi V. 2013. Nitric oxide and cancer: A review. World J. Surg. Oncol. 11, 118. https://doi.org/10.1186/1477-7819-11-118
  3. Chuang JC, Stehr H, Liang Y, Das M, Huang J, Diehn M, Wakelee HA, and Niel W. 2017. ERBB2-mutated metastatic non-small cell lung cancer: response and resistance to targeted therapies. J. Thorac. Oncol. 12, 833-842. https://doi.org/10.1016/j.jtho.2017.01.023
  4. Del Bufalo D, Biroccio A, Leonetti C, and Zupi G. 1997. BCL2 Overexpression enhances the metastatic potential of a human breast cancer line. FASEB J. 11, 947-953. https://doi.org/10.1096/fasebj.11.12.9337147
  5. Egeblad M and Werb Z. 2002. New function for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2, 161-174. https://doi.org/10.1038/nrc745
  6. Foekens JA, Peters HA, Look MP, Portengen H, Schmitt M, Kramer MD, Brunner N, Janicke F, Meijer-van Gelder ME, Henzen-Logmans SC, et al. 2000. The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients. Cancer Res. 60, 636-643.
  7. Hwang JS, Yoo HJ, Song HJ, Kim KK, Chun YJ, Matsui T, and Kim HB. 2011. Inflammation-related signaling pathways implicating TGF${\beta}$ are revealed in the expression profiling of MCF cell treated with fermented soybean, Chungkookjang. Nutr. Cancer 63, 645-652. https://doi.org/10.1080/01635581.2011.551987
  8. Kim JR, Kwon YK, Lee, HY, Heslop-Harrison P, and Cho KH. 2011. Reduction of complex signaling networks to a representative kernel. Sci. Signal. 4, ra35. https://doi.org/10.1126/scisignal.4159ec35
  9. Kischel P, Bellahcene A, Deux B, Lamour V, Doson R, Pauw ED, CLezardin, P, and Castronovo V. 2012. Overexpression of CD9 in human breast cancer cells promote the development of bone metastases. Anticancer Res. 32, 5211-5220.
  10. Lee JJ, Lee DS, and Kim HB. 1999. Fermentation patterns of Chunkookjang and Kanjang by Bacillus licheniformis B1. Korean J. Microbiol. 35, 296-301.
  11. Lee WH, Wu HM, Lee CG, Sung DI, Song HJ, Matsui T, Kim HB, and Kim SG. 2014. Specific oligopeptides in fermented soybean extract inhibit NF-${\kappa}B$-dependent iNOS and cytokine induction by toll-like receptor ligands. J. Med. Food 17, 1239-1246. https://doi.org/10.1089/jmf.2013.3070
  12. Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, et al. 2008. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27, 4702-4711. https://doi.org/10.1038/onc.2008.109
  13. Matsui T, Yoo HJ, Hwang JS, Lee DS, and Kim HB. 2004. Isolation of angiotensin-1-converting enzyme inhibitory peptide from Chungkookjang. Korean J. Microbiol. 40, 355-358.
  14. Moquet-Torcy G, Tolza C, Peachaczyk M, and Jariel-Encontre I. 2014. Transcriptional complexity and roles of Fra-1/AP-1 at uPA/Plau locus in aggressive breast cancer. Nucleic Acids Res. 42, 11011-11024. https://doi.org/10.1093/nar/gku814
  15. O'shea C, McKie N, Buggy Y, Duggan C, Hill AD, McDerMott E, O'Higgins N, and Duffy MJ. 2003. Expression of ADAM-9 mRNA and protein in human breast cancer. Int. J. Cancer 105, 745-761.
  16. Sung DI, Park J, Kang CK, and Kim HB. 2015. Peptide H reduces TNF${\alpha}$ expression in human breast cancer MDA-MB-231 cells. Korean J. Microbiol. 51, 308-311. https://doi.org/10.7845/kjm.2015.5028
  17. Vizoso FJ, Gonzalez LO, Corte MD, Rodriguez JC, Vazquez J, Lamelas ML, Junquera S, Merino AM, and Garcia-Muniz JL. 2007. Study of matrix metalloproteinases and their inhibitors in breast cancer. Br. J. Cancer 96, 903-911. https://doi.org/10.1038/sj.bjc.6603666
  18. Weigelt B, Peterse JL, and van't Veer LJ. 2005. Breast cancer metastasis: markers and models. Nat. Rev. Cancer 5, 591-602. https://doi.org/10.1038/nrc1670