VCAP

Bulk mRNA-Sequencing Data of the Estrogen and Androgen Responses in the Human Prostate Cancer Cell Line VCaP

Estrogen signaling in prostate cancer (PCa) is under-investigated compared to well-established androgen dependence. VCaP cells, expressing wild-type AR and ERα, are ideal for investigating these hormonal interactions. Lafront et al. generated a transcriptomic atlas of androgen and/or estrogen-dependent transcriptional changes in VCaP cells using bulk mRNA-seq.

VCaP cells were treated with androgens and/or estrogens for 24 h, mRNA purified, sequenced, and aligned to the human transcriptome. Transcriptomic changes were analyzed after quantification. The raw data were submitted to the Gene Expression Omnibus (GEO) repository and can be found using the GSE256370 reference number. The dataset contains 12 samples (exact number of four treatment groups: control, R1881 [synthetic androgen], estradiol and estradiol + R1881, with three replicates per group) and, here, were used to test the downregulated transcriptional response upon stimulation by androgen and estrogen with the GSEA tool (Fig. 1).

Androgen- and PKA Signaling-Induced Changes in the Proteomic Profile of VCaP Cells and Identification of Differentially Expressed Proteins

Androgen signaling is crucial in prostate cancer, but resistance leads to CRPC, where PKA may bypass androgen dependence. The key proteins involved remain unknown. You’s team aims to identify proteins regulated by androgen and PKA signaling in VCaP prostate cancer cells, uncovering potential molecular mechanisms behind CRPC progression and therapeutic targets.

VCaP cells were treated with androgen or forskolin (activator of PKA) then subjected to proteomic analysis to quantify the differentially expressed proteins. In total, 113 protein spots that have different expression between the control and DHT or FSK were detected. Among these, eight spots display significant changes in density (> 1.5-fold changes in expression, p < 0.05). These eight differentially expressed proteins (Fig. 2) were significantly increased in response to DHT or FSK in three repeat experiments (Fig. 3). The proteins were subsequently identified by MS analyses. Three proteins were found to be altered in VCaP cells in response to DHT: LDHB, TUFM and HNRNPH3. Five proteins were specifically increased in response to FSK: OXCT1, ACPP, IMPDH2, CCT2 and HNRNPK. To further understand the functional implication of these proteins, they performed a Gene Ontology (GO) analysis on the cellular location and biological function of the proteins. The GO analysis revealed that all the identified proteins are involved in the metabolic process. Notably, metabolic reprogramming has been linked to AR signaling re/activation and antagonism that drives the progression of CRPC.