Differential Quantitative Proteomics Reveals Key Proteins Related to Phenotypic Changes of Breast Cancer Cells Expressing Progesterone Receptor A

Publication date: Available online 3 December 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Prangwan Pateetin, Trairak Pisitkun, Eileen McGowan, Viroj BoonyaratanakornkitAbstractProgesterone receptor isoforms A and B exert different biological effects in breast cancer cells. Alteration of PRA/PRB ratio is often observed during breast cancer progression. High PRA/PRB ratios in breast cancer patients are associated with resistance to chemotherapy and poor prognosis. While it is well accepted that PRA and PRB regulate different sets of genes, how the expression of PRA and PRB alters breast cancer proteomes has not been fully investigated. To directly investigate the effects of PR isoform expression on the breast cancer proteome, both in the presence and absence of progestin, PRA and PRB were independently stably expressed in T47DC42 PR-null breast cancer cells using a doxycycline (Dox)-regulated promoter. Dox induction dose-dependently increased PRA and PRB expression. Dox-induced PRA and PRB showed normal receptor localization and were transcriptionally active. Differential quantitative proteomic analysis by stable isotope dimethyl labeling was performed to quantitatively examine how PR isoforms altered global breast cancer proteomes. Cells expressing PRA in the absence of progestin were enriched in proteins involved in the TCA cycle and enriched in proteins involved in glycolysis and Heat shock factor -1 (HSF-1) activation in the presence of p...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research