TRANSCRIPTION FACTOR BRN-3α AND PROSTATE CANCER, RELATION WITH HORMONE RECEPTORS AND AKT/M-TOR SIGNALING PATHWAY ACTIVATION
https://doi.org/10.21294/1814-4861-2018-17-1-26-31
Abstract
Introduction. The transcription factor Brn-3α (product of the POU4F1) plays a significant role in carcinogenesis. The purpose of the study was to investigate Brn-3α, AR, ERα expressions in tissues of benign prostatic hyperplasia and prostate cancer as well as to determine their association with AKT/mTOR signaling pathway activation.
Material and methods. The study included 30 patients with locally advanced prostate cancer and 15 patients with benign prostatic hyperplasia. The expression levels of Brn-3α, AR, ERα and the components of AKT/m-TOR signaling pathway were determined using RT-PCR assay.
Results. Overexpression of Brn-3α in prostate cancer tissues was found to be associated with high level of ERα mRNA. High expression of AR was revealed in tissues of benign prostatic hyperplasia and prostate cancer. High expression levels of AKT, m-TOR and PTEN were observed in prostate cancer tissues. However, no significant changes in PTEN mRNA level were found in tissues of prostatic hyperplasia. Conclusion. Brn-3α transcription factor was associated with prostate cancer and accompanied with high expression levels of ERα, AKT and m-TOR.
About the Authors
L. V. Spirina
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical University
Russian Federation
Russian Federation
Lyudmila V. Spirina - MD, DSc, Senior Researcher, Laboratory of Tumor Biochemistry, Cancer Research Institute TNRMC RAS, SPIN-code: 1336-8363. ResercherID: A-7760-2012. Author ID: 36960462500.
5, Kooperativny Str., 634009-Tomsk; Siberian State Medical University
A. K. Gorbunov
Cancer Research Institute, Tomsk National Research Medical Center
Russian Federation
Russian Federation
Alexey K. Gorbunov - MD, Researcher, General Oncology Department, Cancer Research Institute, SPIN-код: 3590-6479.
5, Kooperativny Str., 634009-Tomsk
I. V. Kondakova
Cancer Research Institute, Tomsk National Research Medical Center
Russian Federation
Russian Federation
Irina V. Kondakova - MD, DSc, Professor, Head of Tumor Biochemistry Laboratory, Cancer Research Institute, SPIN-code: 9338-4149. Resercher ID: C-8658-2012. Author ID: 6701872510.
5, Kooperativny Str., 634009-Tomsk
E. M. Slonimskaya
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical University
Russian Federation
Russian Federation
Elena M. Slonimskaya - MD, DSc, Professor, Head of General Oncology Department, Cancer Research Institute TNRMC RAS; Professor of Oncology Department SSMU,SPIN-code: 7763-6417. Researcher ID: C-7405-2012. Author ID: 6603658443.
5, Kooperativny Str., 634009-Tomsk; Siberian State Medical University
E. A. Usynin
Cancer Research Institute, Tomsk National Research Medical Center
Russian Federation
Russian Federation
Evgeny A. Usynin - MD, PhD, Senior Researcher, General Oncology Department, Cancer Research Institute, SPIN-code: 1804-0292. Author ID:56204320500.
5, Kooperativny Str., 634009-TomskReferences
1. Budhram-Mahadeo V., Fujita R., Bitsi S., Sicard P., Heads R. Co-expression of POU4F2/Brn-3b with p53 may be important for controlling expression of pro-apoptotic genes in cardiomyocytes following ischaemic/hypoxic insults. Cell Death Dis. 2014; 5: 1503. doi: 10.1038/cddis.2014.452.
2. Berwick D.C., Diss J.K., Budhram-Mahadeo V.S., Latchman D.S. A simple technique for the prediction of interacting proteins reveals a direct Brn-3a-androgen receptor interaction. J Biol Chem. 2010 May 14; 285 (20): 15286–95. doi: 10.1074/jbc.M109.071456.
3. Stoica J., Franke F.T., Wellstein A., Szubaiko F., List H.-J., Reiter R., Morgan E., Martin M.B., Stoica A. Estradiol Rapidly Activates Akt via the ErbB2 Signaling Pathway. J Biol Chem. 2010 May 14; 285 (20): 15286–95. doi: 10.1074/jbc.M109.071456.
4. Vamesu S. Angiogenesis and ER/PR status in primary breast cancer patients: an analysis of 158 needle core biopsies. Rom J Morphol Embryol. 2007; 48 (1): 25–31.
5. Ahmad N., Kumar R. Steroid hormone receptors in cancer development: A target for cancer therapeutics.Cancer Lett. 2011 Jan 1; 300 (1): 1–9. doi: 10.1016/j.canlet.2010.09.008.
6. Chang C., Lee S.O., Yeh S., Chang T.M. Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver. Oncogene. 2014 Jun 19; 33 (25): 3225–34. doi: 10.1038/onc.2013.274.
7. Wang Y., Romigh T., He X., Orloff M.S., Silverman R.H., Heston W.D., Eng C. Resveratrol regulates the PTEN/AKT pathway through androgen receptor-dependent and -independent mechanisms in prostate cancer cell lines. Hum Mol Genet. 2010 Nov 15; 19 (22): 4319–29. doi: 10.1093/hmg/ddq354.
8. Spirina L.V., Usynin Y.A., Kondakova I.V., Yurmazov Z.A., Slonimskaya E.M., Kolegova E.S. The AKT-mTOR Signalling Pathway in Kidney Cancer Tissues. AIP Conf Proc. 2015; 1688: 080004–1–5.
9. Spirina L.V., Usynin E.A., Kondakova I.V., Yurmazov Z.A., Slonimskaya E.M. Effect of Target Therapy on the Content of Transcription and Growth Factors, Protein Kinase TOR, and Activity of Intracellular Proteases in Patients with Metastatic Renal Cell Carcinoma. Bull Exp Biol Med. 2015; 160 (12): 768–772. [in Russian]
10. Miah S., Catto J. BPH and prostate cancer risk. Indian J Urol. 2014; 30 (2): 214–218. doi: 10.4103/0970-1591.126909.
11. Izumi K., Mizokami A., Lin W.J., Lai K.P., Chang C. Androgen receptor roles in the development of benign prostate hyperplasia. Am J Pathol. 2013; 182 (6): 1942–49. doi: 10.1016/j.ajpath.2013.02.028.
12. Wang J., Eltoum I.E., Lamartiniere C.A. Genistein alters growth factor signaling in transgenic prostate model (TRAMP). Mol Cell Endocrinol. 2004; 219: 171–180.
13. Yeh C.R., Da J., Song W., Fazili A., Yeh S. Estrogen receptors in prostate development and cancer. Am J Clin Exp Urol. 2014; 2 (2): 161–168.
Review
For citations:
Spirina L.V., Gorbunov A.K., Kondakova I.V., Slonimskaya E.M., Usynin E.A. TRANSCRIPTION FACTOR BRN-3α AND PROSTATE CANCER, RELATION WITH HORMONE RECEPTORS AND AKT/M-TOR SIGNALING PATHWAY ACTIVATION. Siberian journal of oncology. 2018;17(1):26-31. (In Russ.) https://doi.org/10.21294/1814-4861-2018-17-1-26-31
Views:
1014
Email this article 
