Androgens play an important role in the development and physiology of the normal prostate as well as in prostate cancer cell proliferation. Comparison of the mRNA expression profiles of control and R1881-treated cultures of LNCaP human prostate cancer cells using cDNA subtraction led to the identification of a novel transcription factor that we named Androgen-Induced bZIP (AIbZIP) protein. AIbZIP is a 395 aa protein with homology to cyclic AMP-responsive element binding protein/activating transcription factor transcription factors. It contains an NH₂-terminal activation domain, a central bZIP domain, and a COOH-terminal transmembrane domain. The AIbZIP gene is localized on chromosome 1q21.3 and consists of 10 exons. A major 1.7-kb transcript was detected exclusively in the prostate as well as in breast and prostate cancer cell lines. Androgens up-regulate AIbZIP mRNA and protein levels in a dose-dependent manner. The kinetics of AIbZIP mRNA up-regulation and the results of experiments with cycloheximide suggest that AIbZIP may be a delayed response gene. Immunoreactive AIbZIP protein was primarily detected in the cytoplasm of prostatic luminal epithelial cells. Similarly, full-length AIbZIP-green fluorescent protein fusion proteins were localized in the cytoplasm of LNCaP cells, whereas a truncated form of AIbZIP lacking the putative transmembrane domain was exclusively nuclear. Examination of AIbZIP protein and mRNA expression in a series of transurethral resection of the prostate and needle biopsy specimens indicated that AIbZIP is expressed at higher levels in cancerous prostate cells compared with noncancerous prostate cells. The highly tissue-specific expression profile, androgen regulation, chromosomal localization, and expression profile of AIbZIP in prostate tumors suggest that AIbZIP may play an important role in prostate cancer and in androgen receptor signaling in prostate cells. Future studies will confirm a possible relationship between AIbZIP and prostate cancer.