**2.3 SHBG expression in normal prostate tissue and the LNCaP prostate cancer**

**cell line**  Our analyses also included a detailed look at the SHBG expression patterns in normal human prostate tissue and the LNCaP prostate cancer cell line (Nakhla et al, 2009). Focusing on PL, we found that only the eight exon long SHBG transcript is generated in normal prostate tissue. This suggests that alternatively spliced PL–derived species are either not present, that they exist at levels undetectable by our RT-PCR assay, or that they are synthesized in minor cellular populations within normal prostate tissue. Compared to normal liver tissue, quantitative PCR analysis revealed that normal prostate expresses only 1/1000th the abundance of total PL-derived transcripts. Even taking into account the relative complexity of the PL-transcript expression pattern in normal liver, with the SHBG transcript being most abundant, these findings are in concordance with hepatic SHBG being synthesized for global use (plasma), and prostate SHBG being synthesized for local, or intracellular use. Normal prostate revealed a low abundance of transcripts derived from the two upstream promoters we examined. In striking comparison, the LNCaP prostate cancer cell line exhibited a dramatic relative increase in both the number of alternatively spliced transcripts and transcripts from upstream promoters. The reasons behind these differences in SHBG gene transcription profiles are unclear, they could reflect the clonality of LNCaP cells vs. whole prostate tissue, dysregulation of global RNA processing in LNCaP, and/or changes in specific SHBG mRNA processing elements, among other possibilities. Taken together, the SHBG gene may be a valuable provider of diagnostic, prognostic, and predictive biomarkers for individuals with prostate cancer.
