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Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.

Abstract Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.
PMID
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Authors

Mayor MeshTerms

DNA Methylation

Promoter Regions, Genetic

Keywords

BRMS1

Methylation

cancer

epigenetic

human papilloma virus

uterine cervix

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28381193
OWN - NLM
STAT- MEDLINE
DA  - 20170406
DCOM- 20170418
LR  - 20170418
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 4
DP  - 2017 Apr
TI  - Gene promoter methylation and protein expression of BRMS1 in uterine cervix in
      relation to high-risk human papilloma virus infection and cancer.
PG  - 1010428317697557
LID - 10.1177/1010428317697557 [doi]
AB  - Cervical cancer is strongly related to certain high-risk types of human papilloma
      virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor
      suppressor gene, its expression being regulated by DNA promoter methylation in
      several types of cancers. This study aims to evaluate the methylation status of
      BRMS1 promoter in relation to high-risk types of human papilloma virus infection 
      and the development of pre-cancerous lesions and describe the pattern of BRMS1
      protein expression in normal, high-risk types of human papilloma virus-infected
      pre-cancerous and malignant cervical epithelium. We compared the methylation
      status of BRMS1 in cervical smears of 64 women with no infection by high-risk
      types of human papilloma virus to 70 women with proven high-risk types of human
      papilloma virus infection, using real-time methylation-specific polymerase chain 
      reaction. The expression of BRMS1 protein was described by immunohistochemistry
      in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices.
      Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk
      types of human papilloma virus infection and was less frequent in smears with
      high-risk types of human papilloma virus (11.4%) and in women with pathological
      histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected 
      also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1
      protein staining in normal high-risk types of human papilloma virus-free cervix, 
      in cervical intraepithelial neoplasias, and in malignant tissues, where staining 
      was occasionally also cytoplasmic. In cancer, expression was stronger in the more
      differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and
      aberrant protein expression seem to be related to high-risk types of human
      papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further
      investigation.
FAU - Panagopoulou, Maria
AU  - Panagopoulou M
AD  - 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace,
      Alexandroupolis, Greece.
FAU - Lambropoulou, Maria
AU  - Lambropoulou M
AD  - 2 Laboratory of Histology-Embryology, Medical School, Democritus University of
      Thrace, Alexandroupolis, Greece.
FAU - Balgkouranidou, Ioanna
AU  - Balgkouranidou I
AD  - 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace,
      Alexandroupolis, Greece.
AD  - 3 Department of Oncology, Medical School, Democritus University of Thrace,
      Alexandroupolis, Greece.
FAU - Nena, Evangelia
AU  - Nena E
AD  - 4 Laboratory of Hygiene and Environmental Protection, Medical School, Democritus 
      University of Thrace, Alexandroupolis, Greece.
FAU - Karaglani, Makrina
AU  - Karaglani M
AD  - 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace,
      Alexandroupolis, Greece.
FAU - Nicolaidou, Christina
AU  - Nicolaidou C
AD  - 2 Laboratory of Histology-Embryology, Medical School, Democritus University of
      Thrace, Alexandroupolis, Greece.
FAU - Asimaki, Anthi
AU  - Asimaki A
AD  - 5 Fourth University Clinic of Obstetrics and Gynecology, Hippokrateion Hospital, 
      Aristotle University of Thessaloniki, Thessaloniki, Greece.
FAU - Konstantinidis, Theocharis
AU  - Konstantinidis T
AD  - 4 Laboratory of Hygiene and Environmental Protection, Medical School, Democritus 
      University of Thrace, Alexandroupolis, Greece.
FAU - Constantinidis, Theodoros C
AU  - Constantinidis TC
AD  - 4 Laboratory of Hygiene and Environmental Protection, Medical School, Democritus 
      University of Thrace, Alexandroupolis, Greece.
FAU - Kolios, George
AU  - Kolios G
AD  - 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace,
      Alexandroupolis, Greece.
FAU - Kakolyris, Stylianos
AU  - Kakolyris S
AD  - 3 Department of Oncology, Medical School, Democritus University of Thrace,
      Alexandroupolis, Greece.
FAU - Agorastos, Theodoros
AU  - Agorastos T
AD  - 5 Fourth University Clinic of Obstetrics and Gynecology, Hippokrateion Hospital, 
      Aristotle University of Thessaloniki, Thessaloniki, Greece.
FAU - Chatzaki, Ekaterini
AU  - Chatzaki E
AD  - 1 Laboratory of Pharmacology, Medical School, Democritus University of Thrace,
      Alexandroupolis, Greece.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (BRMS1 protein, human)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cervical Intraepithelial Neoplasia/etiology
MH  - Cervix Uteri/*metabolism
MH  - *DNA Methylation
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Middle Aged
MH  - Papillomavirus Infections/*complications
MH  - *Promoter Regions, Genetic
MH  - Repressor Proteins/analysis/*genetics
MH  - Risk
MH  - Uterine Cervical Neoplasms/*etiology
OTO - NOTNLM
OT  - BRMS1
OT  - Methylation
OT  - cancer
OT  - epigenetic
OT  - human papilloma virus
OT  - uterine cervix
EDAT- 2017/04/07 06:00
MHDA- 2017/04/19 06:00
CRDT- 2017/04/07 06:00
AID - 10.1177/1010428317697557 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Apr;39(4):1010428317697557. doi: 10.1177/1010428317697557.

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