Analysis of Differential Gene Expression in Androgen-Independent Clones Derived from the MyCaP PCa Cell Line

Androgen deprivation therapy (ADT) is a primary treatment strategy for prostate cancer (PCa), yet many tumors eventually develop androgen independence, leading to treatment resistance. To investigate the molecular changes underlying this transition, we analyzed differential gene expression in four androgen-independent (AI) clones derived from the Myc-CaP prostate cancer cell line using RNA sequencing. Gene expression profiles were compared to the parental Myc-CaP line, and differentially expressed genes (DEGs) were identified using DESeq2 and edgeR. The AI clones exhibited significant downregulation of senescence-associated genes, including Ezh2 and lamin B1, suggesting a loss of senescence-related chromatin repression. Additionally, upregulation of Wnt pathway genes (Wnt2/3/4/6) was observed, although key Hippo pathway regulators YAP (Yap1) and TAZ (Wwtr1) remained unchanged, implying a Hippo-independent role of Wnt signaling in androgen independence. Notably, Igfbp5, a modulator of insulin-like growth factor signaling, was highly upregulated in all AI clones, alongside increased expression of pro-angiogenic factors haptoglobin (Hp) and angiotensinogen (Agt). These findings suggest that chromatin accessibility, growth factor signaling, and angiogenesis play key roles in the development of androgen independence. The observed changes highlight potential therapeutic targets, including CDK inhibitors, Wnt and IGF pathway modulators, and HDAC inhibitors, for combating resistance in androgen-independent prostate cancer.