Sarah M Bernhardt1,2, Pallave Dasari1,2, Danielle J Glynn1,2, Amanda R Townsend1,3, Timothy J Price1,3, Wendy V Ingman4,5. 1. Discipline of Surgery, Adelaide Medical School, The Queen Elizabeth Hospital, University of Adelaide, DX465702, 28 Woodville Rd, Woodville, Adelaide, SA, 5011, Australia. 2. Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia. 3. Department of Medical Oncology, The Queen Elizabeth Hospital, Adelaide, SA, Australia. 4. Discipline of Surgery, Adelaide Medical School, The Queen Elizabeth Hospital, University of Adelaide, DX465702, 28 Woodville Rd, Woodville, Adelaide, SA, 5011, Australia. wendy.ingman@adelaide.edu.au. 5. Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia. wendy.ingman@adelaide.edu.au.
Abstract
PURPOSE: Protein biomarkers estrogen receptor (ER), progesterone receptor (PR), and marker of proliferation (Ki67) are routinely assessed by immunohistochemistry to guide treatment decisions for breast cancer. Now, quantification of mRNA encoding these proteins is being adopted in the clinic. However, mRNA and protein biomarkers may be differentially regulated by fluctuations in estrogen and progesterone that occur across the menstrual cycle in premenopausal breast cancer patients. This study aimed to compare how estrogen and progesterone affect mRNA and protein biomarker expression in hormone-responsive breast cancer cells. METHODS: Hormone-responsive ZR-75-1 and T-47D human breast cancer cell lines were xenografted into the mammary fat pad of BALB/c nude mice supplemented with estrogen. Progesterone or vehicle was administered prior to dissection of tumors. Protein expression of ER, PR and Ki67 was quantified by immunohistochemistry, and mRNA encoding these proteins, ESR1, PGR and KI67, respectively, was quantified by real-time PCR. mRNA expression was also quantified in breast cancer cell lines treated with estrogen and progesterone in vitro. RESULTS: In T-47D-xenografted tumors, estrogen and progesterone treatment reduced PGR and KI67 mRNA expression, and reduced PR and Ki67 protein positivity, compared to estrogen treatment alone. In ZR-75-1 xenografted tumors, no significant differences in protein or mRNA biomarker expression were observed. In vitro, estrogen and progesterone co-treatment significantly reduced ESR1 and PGR mRNA expression in both T-47D and ZR-75-1 cell lines. CONCLUSIONS: Estrogen and progesterone similarly affect mRNA and protein biomarker expression in hormone-responsive breast cancer xenografts. Further research is needed to investigate concordance between protein and mRNA biomarkers in premenopausal breast cancer.
PURPOSE: Protein biomarkers estrogen receptor (ER), progesterone receptor (PR), and marker of proliferation (Ki67) are routinely assessed by immunohistochemistry to guide treatment decisions for breast cancer. Now, quantification of mRNA encoding these proteins is being adopted in the clinic. However, mRNA and protein biomarkers may be differentially regulated by fluctuations in estrogen and progesterone that occur across the menstrual cycle in premenopausal breast cancerpatients. This study aimed to compare how estrogen and progesterone affect mRNA and protein biomarker expression in hormone-responsive breast cancer cells. METHODS: Hormone-responsive ZR-75-1 and T-47D humanbreast cancer cell lines were xenografted into the mammary fat pad of BALB/c nude mice supplemented with estrogen. Progesterone or vehicle was administered prior to dissection of tumors. Protein expression of ER, PR and Ki67 was quantified by immunohistochemistry, and mRNA encoding these proteins, ESR1, PGR and KI67, respectively, was quantified by real-time PCR. mRNA expression was also quantified in breast cancer cell lines treated with estrogen and progesterone in vitro. RESULTS: In T-47D-xenografted tumors, estrogen and progesterone treatment reduced PGR and KI67 mRNA expression, and reduced PR and Ki67 protein positivity, compared to estrogen treatment alone. In ZR-75-1 xenografted tumors, no significant differences in protein or mRNA biomarker expression were observed. In vitro, estrogen and progesterone co-treatment significantly reduced ESR1 and PGR mRNA expression in both T-47D and ZR-75-1 cell lines. CONCLUSIONS: Estrogen and progesterone similarly affect mRNA and protein biomarker expression in hormone-responsive breast cancer xenografts. Further research is needed to investigate concordance between protein and mRNA biomarkers in premenopausal breast cancer.
Entities:
Keywords:
Breast cancer; Estrogen; Gene biomarkers; Menstrual cycle; Progesterone
Authors: E Senkus; S Kyriakides; S Ohno; F Penault-Llorca; P Poortmans; E Rutgers; S Zackrisson; F Cardoso Journal: Ann Oncol Date: 2015-09 Impact factor: 32.976
Authors: A S Coates; E P Winer; A Goldhirsch; R D Gelber; M Gnant; M Piccart-Gebhart; B Thürlimann; H-J Senn Journal: Ann Oncol Date: 2015-05-04 Impact factor: 32.976
Authors: P M Ravdin; S Green; T M Dorr; W L McGuire; C Fabian; R P Pugh; R D Carter; S E Rivkin; J R Borst; R J Belt Journal: J Clin Oncol Date: 1992-08 Impact factor: 44.544
Authors: Torsten A Hopp; Heidi L Weiss; Susan G Hilsenbeck; Yukun Cui; D Craig Allred; Kathryn B Horwitz; Suzanne A W Fuqua Journal: Clin Cancer Res Date: 2004-04-15 Impact factor: 12.531
Authors: Carey K Anders; David S Hsu; Gloria Broadwater; Chaitanya R Acharya; John A Foekens; Yi Zhang; Yixin Wang; P Kelly Marcom; Jeffrey R Marks; Phillip G Febbo; Joseph R Nevins; Anil Potti; Kimberly L Blackwell Journal: J Clin Oncol Date: 2008-07-10 Impact factor: 44.544
Authors: Jennifer L Gnerlich; Anjali D Deshpande; Donna B Jeffe; Allison Sweet; Nick White; Julie A Margenthaler Journal: J Am Coll Surg Date: 2009-01-21 Impact factor: 6.113
Authors: C Davies; J Godwin; R Gray; M Clarke; D Cutter; S Darby; P McGale; H C Pan; C Taylor; Y C Wang; M Dowsett; J Ingle; R Peto Journal: Lancet Date: 2011-07-28 Impact factor: 79.321
Authors: Hanna Fredholm; Sonja Eaker; Jan Frisell; Lars Holmberg; Irma Fredriksson; Henrik Lindman Journal: PLoS One Date: 2009-11-11 Impact factor: 3.240