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Elevated Oestrogen Receptor Splice Variant ERαΔ5 Expression in Tumour-adjacent Hormone-responsive Tissue

DOI: 10.3390/ijerph7113871

Keywords: endometrial cancer, oestrogen receptor, prostate cancer, real-time RT PCR, splice variant

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Abstract:

Susceptibility to prostate or endometrial cancer is linked with obesity, a state of oestrogen excess. Oestrogen receptor (ER) splice variants may be responsible for the tissue-level of ER activity. Such micro-environmental regulation may modulate cancer initiation and/or progression mechanisms. Real-time reverse transcriptase (RT) polymerase chain reaction (PCR) was used to quantitatively assess the levels of four ER splice variants ( ER α Δ 3, ER α Δ 5, ER β2 and ER β 5), plus the full-length parent isoforms ER α and ER β 1, in high-risk [tumour-adjacent prostate ( n = 10) or endometrial cancer ( n = 9)] vs. low-risk [benign prostate ( n = 12) or endometrium ( n = 9)], as well as a comparison of UK ( n = 12) vs. Indian ( n = 15) benign prostate. All three tissue groups expressed the ER splice variants at similar levels, apart from ER α Δ 5. This splice variant was markedly raised in all of the tumour-adjacent prostate samples compared to benign tissues. Immunofluorescence analysis for ER β2 in prostate tissue demonstrated that such splice variants are present in comparable, if not greater, amounts as the parent full-length isoform. This small pilot study demonstrates the ubiquitous nature of ER splice variants in these tissue sites and suggests that ER α Δ5 may be involved in progression of prostate adenocarcinoma.

References

[1]  Whittemore, AS; Kolonel, LN; Wu, AH; John, EM; Gallagher, RP; Howe, GR; Burch, JD; Hankin, J; Dreon, DM; West, DW; Teh, C-Z; Paffenbarger, RS, Jr. Prostate cancer in relation to diet, physical activity, and body size in Blacks, Whites, and Asians in the United States and Canada. J. Natl. Cancer Inst?1995, 87, 652–661.
[2]  Dey, S; Hablas, A; Seifeldin, IA; Ismail, K; Ramadan, M; El-Hamzawy, H; Wilson, ML; Banerjee, M; Boffetta, P; Harford, J; Merajver, SD; Soliman, AS. Urban-rural differences of gynaecological malignancies in Egypt (1999–2002). BJOG?2010, 117, 348–355.
[3]  Yang, C-Y; Hsieh, Y-L. The Relationship between Population Density and Cancer Mortality in Taiwan. Jpn. J. Cancer Res?1998, 89, 355–360.
[4]  Khan, N; Afaq, F; Mukhtar, H. Lifestyle as risk factor for cancer: Evidence from human studies. Cancer Lett?2010, 293, 133–143.
[5]  Rieck, G; Fiander, A. The effect of lifestyle factors on gynaecological cancer. Best Pract. Res. Clin. Obstet. Gynaecol?2006, 20, 227–251.
[6]  Sorosky, J. Endometrial Cancer. Obstet. Gynecol?2008, 111, 436–477.
[7]  Singh, PB; Matanhelia, SS; Martin, FL. A potential paradox in prostate adenocarcinoma progression: Oestrogen as the initiating driver. Eur. J. Cancer?2008, 44, 928–936.
[8]  Setlur, SR; Mertz, KD; Hoshida, Y; Demichelis, F; Lupien, M; Perner, S; Sboner, A; Pawitan, Y; Andren, O; Johnson, LA; Tang, J; Adami, H-O; Calza, S; Chinnaiyan, AM; Rhodes, D; Tomlins, S; Fall, K; Mucci, LA; Kantoff, PW; Stampfer, MJ; Andersson, S-O; Varenhorst, E; Johansson, J-E; Brown, M; Golub, TR; Rubin, MA. Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer. J. Natl. Cancer Inst?2008, 100, 815–825.
[9]  Simpson, ER; Clyne, C; Rubin, G; Boon, WC; Robertson, K; Britt, K; Speed, C; Jones, M. Aromatase - a brief overview. Annu. Rev. Physiol?2002, 64, 93–127.
[10]  Taylor, SE; Martin-Hirsch, PL; Martin, FL. Oestrogen receptor splice variants in the pathogenesis of disease. Cancer Lett?2010, 288, 133–148.
[11]  Koduri, S; Goldhar, AS; Vonderhaar, BK. Activation of vascular endothelial growth factor (VEGF) by the ER-α variant, ERΔ3. Breast Cancer Res. Treat?2006, 95, 37–43.
[12]  Bollig, A; Miksicek, RJ. An estrogen receptor-α splicing variant mediates both positive and negative effects on gene transcription. Mol. Endocrinol?2000, 14, 634–649.
[13]  Leung, Y-K; Mak, P; Hassan, S; Ho, S-M. Estrogen receptor (ER)-β isoforms: a key to understanding ER-β signalling. Proc. Natl. Acad. Sci. USA?2006, 103, 13162–13167.
[14]  Girault, I; Andrieu, C; Tozlu, S; Spyratos, F; Bièche, I; Lidereau, R. Altered expression pattern of alternatively spliced estrogen receptor β transcripts in breast carcinoma. Cancer Lett?2004, 215, 101–112.
[15]  Poola, I; Abraham, J; Baldwin, K; Saunders, A; Bhatnagar, R. Estrogen receptors beta4 and beta5 are full length functionally distinct ERβ isoforms. Endocrine?2005, 27, 227–238.
[16]  Rey, JM; Pujol, P; Dechaud, H; Edouard, E; Hedon, B; Maudelonde, T. Expression of oestrogen receptor-α splicing variants and oestrogen receptor-β in endometrium of infertile patients. Mol. Hum. Reprod?1998, 4, 641–647.
[17]  Marshburn, PB; Zhang, J; Bahrani–Mostafavi, Z; Mostafavi, BZ; Marroum, M-C; Mougeot, J-LC; Roshon, MJ. Estrogen receptor-α messenger RNA variants that lack exon 5 or exon 7 are coexpressed with wild-type form in human endometrium during all phases of the menstrual cycle. Am. J. Obstet Gynecol?2004, 191, 626–633.
[18]  Skrzypczak, M; Bieche, I; Szymczak, S; Tozlu, S; Lewan Ddowowski, S; Girault, I; Radwanska, K; Szczylik, C; Jakowicki, J; LidereauI, R; Kaczmarek, L. Evaluation of mRNA expression of estrogen receptor β and its isoforms in human normal and neoplastic endometrium. Int. J. Cancer?2004, 110, 783–787.
[19]  Leung, Y-K; Lam, H-M; Wu, S; Song, D; Levin, L; Cheng, L; Wu, C-L; Ho, S-M. Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion. Endocr. Relat. Cancer?2010, 17, 675–689.
[20]  Singh, MN; Stringfellow, HF; Taylor, SE; Ashton, KM; Ahmad, M; Abdo, KR; El-Agnaf, OMA; Martin-Hirsch, PL; Martin, FL. Elevated expression of CYP1A1 and γ-SYNUCLEIN in human ectopic (ovarian) endometriosis compared with eutopic endometrium. Mol. Hum. Reprod?2008, 14, 655–663.
[21]  Singh, PB; Ragavan, N; Ashton, KM; Basu, P; Nadeem, SM; Nicholson, CM; Krishna, RKG; Matanhelia, SS; Martin, FL. Quantified gene expression levels for phase I/II metabolizing enzyme and estrogen receptor levels in benign prostate from cohorts designated as high-risk (UK) versus low-risk (India) for adenocarcinoma at this organ site: a preliminary study. Asian J. Androl?2010, 12, 203–214.
[22]  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. Gynecol. Oncol?2007, 106, 407–412.
[23]  Yared, E; McMillan, TJ; Martin, FL. Genotoxic effects of oestrogens in breast cells detected by the micronucleus assay and the Comet assay. Mutagenesis?2002, 17, 345–352.
[24]  John, K; Ragavan, N; Pratt, MM; Singh, PB; Al-Buheissi, S; Matanhelia, SS; Phillips, DH; Poirier, MC; Martin, FL. Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon–DNA adduct levels in human prostate. Prostate?2009, 69, 505–519.
[25]  Martin, FL; Patel, II; Sozeri, O; Singh, PB; Ragavan, N; Nicholson, CM; Frei, E; Meinl, W; Glatt, H; Phillips, DH; Arlt, VM. Constitutive expression of bioactivating enzymes in normal human prostate suggests a capability to activate pro-carcinogens to DNA-damaging metabolites. Prostate?2010, 70, 1586–1599.
[26]  Martin, FL; Kelly, JG; Llabjani, V; Martin–Hirsch, PL; Patel, II; Trevisan, J; Fullwood, NJ; Walsh, MJ. Distinguishing cell types or populations based on the computational analysis of their infrared spectra. Nat. Protoc?2010, 5, 1748–1760.

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