Comparison of hormone-induced mRNA and protein biomarker expression changes in breast cancer cells

• Published in: Breast cancer research and treatment Vol. 187; no. 3; pp. 681 - 693
• Main Authors: Bernhardt, Sarah M., Dasari, Pallave, Glynn, Danielle J., Townsend, Amanda R., Price, Timothy J., Ingman, Wendy V.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2021; Springer; Springer Nature B.V
• Subjects: Biomarkers; Breast cancer; Cancer; Cancer cells; Cancer research; Care and treatment; Comparative analysis; Estrogen; Estrogen receptors; Estrogens; Gene expression; Hormones; Immunohistochemistry; Medicine; Medicine & Public Health; Menopause; Menstrual cycle; Messenger RNA; Oncology; Oncology, Experimental; Preclinical Study; Progesterone; Proteins; Tumor cell lines; Tumors; Xenografts; Breast cancer; Progesterone; Menstrual cycle; Estrogen; Gene biomarkers
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-021-06254-z

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.