Analysis of correlation between transcription activity of estrogen-dependent genes of cytochrome P450 and profile of estrogen receptor in endometrial adenocarcinoma
 
More details
Hide details
1
Department of Gynaecological and Obstetrics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
 
2
Department of Medical Genetics, Faculty of Pharmacentical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
 
 
Corresponding author
Agnieszka Jęda-Golonka   

Katedra i Klinika Ginekologii i Położnictwa, Wydział Nauk Medycznych w Katowicach, Śląski Uniwersytet Medyczny w Katowicach, ul. Medyków 14, 40-752 Katowice, Polska
 
 
Ann. Acad. Med. Siles. 2020;74:24-39
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Studies show that the development of endometrial cancer is associated with the activity of estrogen-dependent genes, whose action is conditioned by the presence of estrogen receptors (ER). Analysis of the transcriptional activity of the genes which code ERs as well as the concentration profile of their isoforms could help to understand the mechanism of estrogen activity on the risk of endometrial cancer occurrence, as well as the mechanisms involved in its development and spread. The aim of the conducted studies was to compare the transcriptional activity of the genes coding ER-alpha and ER-beta estrogen receptors, determine the types of post-transcription modifications of ER mRNA in endometrial adenocarcinoma and normal endometrium as well as determine the transcriptome of estrogen-dependent genes of cytochrome P450.

Material and methods:
Extraction of the total RNA from 47 endometrium samples was performed with the TRIzol reagent (Invitrogen). The expression profile of the estrogen-dependent genes of cytochrome P450 was determined using the HG-U133A (Affymetrix) oligonucleotide microarray technique from among 22,283 IDs of mRNA IDs. The QRT-PCR reaction for quantification of the mRNA of estrogen receptors was performed using an ABI PRISMTM 7700 (TaqMan) sequence detector. For the QRT-PCR reaction, oligonucleotide starter sequences to detect the ER-alpha and ER-beta mRNA isoforms were designed using Primer ExpressTM Version 1.0 software.

Results:
In the presented work, it was found that estrogen receptor gene expression occurs in normal endometrium as well as in endometrial adenocarcinoma, and the dominating type is ER-alpha. The transcriptional activity of the ER-alpha and ER-beta genes decreases in adenocarcinoma with a simultaneous increase in the transcriptional activity ratio. The ER-alpha/delta5 isoform dominates in endometrial cancer. Statistical analysis conducted in the GeneSpring 11.5 programme showed that from the group of 91 mRNA IDs of the genes of cytochrome P450, 5 mRNA IDs differentiate, for p <0.5 and FC(log2) > 1.5. In the presented work, it was found that the expression of estrogen receptor genes occurs in normal endometrium and endometrial adenocarcinoma, and the dominant type is ER-alpha. The transcriptional activity of the ER-alpha and ER-beta genes decreases in adenocarcinoma, while the transcriptional activity index increases. In endometrial cancer, the ER-alpha/delta5 isoform dominates. Statistical analysis conducted in GeneSpring 11.5 showed that from the group 91 ID mRNA of cytochrome P450 genes, 5 ID mRNA is differentiating, for p < 0.5 and FC (log2) > 1.5.

Conclusions:
The presence of such a transcriptional profile of the studied genes in endometrial adenocarcinoma may indicate that post-transcriptional modifications of estrogen receptors are associated with changes triggering carcinogenesis.

REFERENCES (26)
1.
Raporty na podstawie danych Centrum Onkologii: www.epid.coi.waw.pl/krn [dostęp: 31.10.2016].
 
2.
Siegel R.L., Miller K.D., Jemal A. Cancer statistics 2016. CA Cancer J. Clin. 2016; 66(1): 7–30, doi: 10.3322/caac.21332.
 
3.
Felix A.S., Weissfeld J.L., Stone R.A., Bowser R., Chivukula M., Edwards R.P., Linkov F. Factors associated with Type I and Type II endometrial cancer. Cancer Causes Control. 2010; 21(11): 1851–1856, doi: 10.1007/s10552-010-9612-8.
 
4.
Woodruff J.D., Pickar J.H. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate conjugated estrogens alone. The Menopause Study Group. Am. J. Obstet. Gynecol. 1994; 170 (5 Pt1): 1213–1273, doi: 10.1016/s0002-9378(94)70129-6.
 
5.
Alquobaili F., Miller S.A., Muhie S., Day A., Jett M., Hammamieh R. Estrogen receptor-dependent genomic expression profiles in breast cancer cells in response to fatty acids. J. Carcinog. 2010; 8: 17, doi: 10.4103/1477-3163.59539.
 
6.
Kumar R., Zakharov M.N., Khan S.H., Miki R., Jang H., Toraldo G., Singh R., Bhasin S., Jasuja R. The dynamic structure of the estrogen receptor. J. Amino Acids 2011: 812540, doi: 10.4061/2011/812540.
 
7.
Zielniok K., Gajewska M., Motyl T. Molekularne aspekty działania 17β-estradiolu i progesteronu w komórkowych szlakach sygnałowych. Postepy Hig. Med. Dosw. (online) 2014; 68: 777–792, doi: 10.5604/17322693.1108390.
 
8.
Groenendijk F.H., Zwart W., Floore A., Akbari S., Bernards R. Estrogen receptor splice variants as a potential source of false-positive estrogen receptor status in breast cancer diagnostics. Breast Cancer Res. Treat. 2013; 140(3): 475–484, doi: 10.1007/s10549-013-2648-1.
 
9.
Fujii-Kurijama Y., Mimura J. Molecular mechanism of AhR functions in the regulation of cytochrome P450 genes. Biochem. Biophys. Res. Commun. 2005; 338(1): 311–317, doi: 10.1016/j.bbrc.2005.08.162.
 
10.
Honkakoski P., Negishi M. Regulation of cytochrome P450 (CYP) genes by nuclear receptors. Biochem. J. 2000; 347(Pt2): 321–337.
 
11.
Tomaszewski P., Kubiak-Tomaszewska G., Łukaszkiewicz J., Pachecka J. Cytochrome P450 polymorphism-molecular, metabolic, and pharmacogenetic aspects. Influence of CYP genetic polymorphism on population differentiation of drug metabolism phenotype. Acta Pol. Pharm. 2008; 65(3): 319–329.
 
12.
Iwao K., Miyoshi Y., Egawa c., Ikeda N., Noguchi S. Quantitative analysis of estrogen receptor mRNA and its variants in human breast cancers. Int. J. Cancer 2000; 88: 733–736.
 
13.
Whitehead M., Fraser D. The effects of estrogens and progestogens on the endometrium: modern approach to treatment. Obstet. Gynecol. Clin. North Am. 1987; 14(1): 299–302.
 
14.
Licznerska B., Baer-Dubowska W. Estrogen intracrinology: therapy and chemoprevention of breast cancer. Postepy Hig. Med. Dosw. (online) 2010; 64: 220–230.
 
15.
Salama S.A., Kamel M., Awad M., Hakim A., Nasser B., Al‐Hendy A., Botting S. Catecholestrogens induce oxidative stress and malignant transformation in human endometrial glandular cells: protective effect of catechol-O-methyltransferase. Int. J. Cancer 2008; 123(6): 1246–1254, doi: 10.1002/ijc.23653.
 
16.
Fuhrman B., Schairer C., Gail C., Boyd-Morin J., Xu X., Sue L.Y., Buys S.S., Isaacs C., Keefer L.K., Veenstra T.D., Berg C.D., Hoover R.N., Ziegler R.G. Estrogen Metabolism and Risk of Breast Cancer in Postmenopausal Women. J. Natl. Cancer Inst. 2012; 104: 326–338, doi: 10.1093/jnci/djr531.
 
17.
Hirata S., Yamada Mouri N., Nara M., Takazawa N., Ito H., Kato J. Presence of alternativeli spliced-estrogen receptor mRNA variants in normal human uterine endometrium and endometria cancer. Endoc. J. 1995; 42(2): 289–293, doi: 10.1507/endocrj.42.289.
 
18.
Iwao K., Miyoshi Y., Egawa C., Ikeda N., Noguchi S. Quantitative analysis of estrogen receptor-beta mRNA and its variants in human brest cancer. Int. J. Cancer. 2000; 88(5): 733–736, doi: 10.1002/1097-0215(20001201)88:5<733::aid-ijc8>3.0.co;2-m.
 
19.
Pettersson K., Gustafsson J.A. Role of estrogen receptor beta in estrogen action. Annu. Rev. Physiol. 2001; 63: 165–192, doi: 10.1146/annurev.physiol.63.1.165.
 
20.
Kato K., Houriochi S., Terao S., Ueoka Y., Nishida J., Mori D., Yoshikawa Y. Wake N. Relevance of ER to the development of endometrial hyperplasia and adenocarcinoma. Breast Cancer. 1999; 6(4): 312–319, doi: 10.1007/bf02966446.
 
21.
Witek A., Paul-Samojedny M., Stojko R., Seifert B., Mazurek U. Coexpression index of estrogen receptor alpha mRNA isoforms in simple, complex hyperplasia without atypia, complex atypical hyperplasia and adenocarcinoma. Gynecologic Oncology 2007; 106(2): 407–412, 10.1016/j.ygyno.2007.04.035.
 
22.
Al-Bader M., Ford C., Al-Ayadh B., Francis I. Analysis of estrogen receptor isoforms and variants in breast cancer cell lines. Exp. Ther. Med. 2011; 2(3): 537–544, doi: 10.3892/etm.2011.226.
 
23.
Fujimoto J., Ichigo s., Hirose R., Sakaguchi H., Tamaya T. Expression of estrogen receptor wild type and exone 5 splicing variany mRNAs in normal and endometriotic endometria during the menstrual cycle. Gynecol. Endocrinol. 1997; 11(1): 11–16, doi: 10.3109/09513599709152310.
 
24.
Lee M.T., Ho S.M., Tarapore P., Chung I., Leung Y.K. Estrogen Receptor β Isoform 5 Confers Sensitivity of Breast Cancer Cell Lines to Chemotherapeutic Agent-Induced Apoptosis through Interaction with Bcl2L12. Neoplasia. 2013; 15(11): 1262–1271, doi: 10.1593/neo.131184.
 
25.
Chi A., Chen C., Chirala M., Younes M. Differential expression of estrogen receptor beta isoforms in human breast cancer tissue. Anticancer Res. 2003; 23 (1A): 211–216.
 
26.
Zhou S. Human CYP39A1, 46A1, and 51A1. In: Zhou S. Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism. CRC Press Taylor & Francis Group 2016, Boca Raton 59.
 
eISSN:1734-025X
Journals System - logo
Scroll to top