PMID- 32560316
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20210216
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 12
DP  - 2020 Jun 17
TI  - Characterization of HLA-G Regulation and HLA Expression in Breast Cancer and 
      Malignant Melanoma Cell Lines upon IFN-gamma Stimulation and Inhibition of DNA 
      Methylation.
LID - 10.3390/ijms21124307 [doi]
LID - 4307
AB  - The potential role of human leukocyte antigen (HLA)-G as a target for new cancer 
      immunotherapy drugs has increased the interest in the analysis of mechanisms by 
      which HLA-G expression is regulated, and how the expression can be manipulated. 
      We characterized HLA expression in breast cancer and malignant melanoma cell 
      lines and investigated the induction of HLA-G expression by two distinct 
      mechanisms: stimulation with interferon (IFN)-gamma or inhibition of methylation by 
      treatment with 5-aza-2'-deoxycytidine (5-aza-dC). The effect of IFN-gamma and 
      5-aza-dC on HLA expression was dependent on the cancer cell lines studied. 
      However, in general, surface expression of HLA class Ia was induced on all cell 
      lines. Surface expression of HLA-G was inconclusive but induction of HLA-G mRNA 
      was prevalent upon treatment with 5-aza-dC and a combination of IFN-gamma and 
      5-aza-dC. IFN-gamma alone failed to induce HLA-G expression in the HLA-G-negative 
      cell lines. The results support that HLA-G expression is regulated partly by DNA 
      methylation. Furthermore, IFN-gamma may play a role in the maintenance of HLA-G 
      expression rather than inducing expression. The study demonstrates the 
      feasibility of manipulating HLA expression and contributes to the exploration of 
      mechanisms that can be potential targets for immunotherapy in breast cancer and 
      malignant melanoma.
FAU - Jorgensen, Nanna
AU  - Jorgensen N
AUID- ORCID: 0000-0003-1109-296X
AD  - Department of Clinical Biochemistry, Centre for Immune Regulation and 
      Reproductive Immunology (CIRRI), The ReproHealth Consortium ZUH, Zealand 
      University Hospital, 4000 Roskilde, Denmark.
AD  - Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen N, 
      Denmark.
FAU - Sayed, Abid
AU  - Sayed A
AUID- ORCID: 0000-0001-7856-5114
AD  - Department of Clinical Biochemistry, Centre for Immune Regulation and 
      Reproductive Immunology (CIRRI), The ReproHealth Consortium ZUH, Zealand 
      University Hospital, 4000 Roskilde, Denmark.
AD  - Department of Science and Environment, Roskilde University, 4000 Roskilde, 
      Denmark.
FAU - Jeppesen, Helene Bjerregaard
AU  - Jeppesen HB
AD  - Department of Clinical Biochemistry, Centre for Immune Regulation and 
      Reproductive Immunology (CIRRI), The ReproHealth Consortium ZUH, Zealand 
      University Hospital, 4000 Roskilde, Denmark.
AD  - Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen N, 
      Denmark.
FAU - Persson, Gry
AU  - Persson G
AD  - Department of Clinical Biochemistry, Centre for Immune Regulation and 
      Reproductive Immunology (CIRRI), The ReproHealth Consortium ZUH, Zealand 
      University Hospital, 4000 Roskilde, Denmark.
FAU - Weisdorf, Iben
AU  - Weisdorf I
AD  - Department of Clinical Biochemistry, Centre for Immune Regulation and 
      Reproductive Immunology (CIRRI), The ReproHealth Consortium ZUH, Zealand 
      University Hospital, 4000 Roskilde, Denmark.
FAU - Funck, Tina
AU  - Funck T
AD  - Department of Clinical Biochemistry, Centre for Immune Regulation and 
      Reproductive Immunology (CIRRI), The ReproHealth Consortium ZUH, Zealand 
      University Hospital, 4000 Roskilde, Denmark.
FAU - Hviid, Thomas Vauvert Faurschou
AU  - Hviid TVF
AD  - Department of Clinical Biochemistry, Centre for Immune Regulation and 
      Reproductive Immunology (CIRRI), The ReproHealth Consortium ZUH, Zealand 
      University Hospital, 4000 Roskilde, Denmark.
AD  - Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen N, 
      Denmark.
LA  - eng
GR  - no number/Den forskningsfremmende pulje, The Faculty of Health and Medical 
      Sciences, University of Copenhagen/
GR  - no number/The Region Zealand Health Sciences Research Foundation and Zealand 
      University Hospital/
PT  - Journal Article
DEP - 20200617
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (HLA-G Antigens)
RN  - 0 (RNA, Messenger)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Alleles
MH  - Breast Neoplasms/*genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Membrane/metabolism
MH  - *DNA Methylation
MH  - Female
MH  - Flow Cytometry
MH  - *Gene Expression Regulation, Neoplastic
MH  - HLA-G Antigens/*genetics/immunology/metabolism
MH  - Humans
MH  - Interferon-gamma/*metabolism/pharmacology
MH  - Melanoma/genetics/metabolism
MH  - RNA, Messenger/genetics
PMC - PMC7352735
OTO - NOTNLM
OT  - DNA methylation
OT  - HLA-G
OT  - breast cancer
OT  - immunoediting
OT  - in vitro modification
OT  - malignant melanoma
COIS- The authors declare no conflict of interest. The funding sponsors had no role in 
      the design, execution, interpretation, or writing of the study.
EDAT- 2020/06/21 06:00
MHDA- 2021/02/17 06:00
PMCR- 2020/06/01
CRDT- 2020/06/21 06:00
PHST- 2020/05/18 00:00 [received]
PHST- 2020/06/11 00:00 [revised]
PHST- 2020/06/13 00:00 [accepted]
PHST- 2020/06/21 06:00 [entrez]
PHST- 2020/06/21 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/06/01 00:00 [pmc-release]
AID - ijms21124307 [pii]
AID - ijms-21-04307 [pii]
AID - 10.3390/ijms21124307 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Jun 17;21(12):4307. doi: 10.3390/ijms21124307.