PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

Abstract

Purpose: We previously reported the isolation and characterization of PrLZ, a novel prostatespecific and androgen-responsive gene of the tumor protein D52 family at chromosome 8q21.1. PrLZ is the only known gene in this locus with prostate specificity. Expression level of PrLZ was elevated specifically in cancer cells, suggesting its association with malignancy. Experimental Design:To define its biological function in the morphogenesis, development, and functional maturation of the prostate gland and to gain further insight into its role in prostate cancer, we examined PrLZ expression in prostate specimens during early embryonic development and in adult tissue. Results: PrLZ first appears in the nuclei of the prostate epithelia at 16 weeks of gestation before its distribution in the cytoplasm at later ages. Its expression peaks at 24 years of age, declines at 31years of age, and maintains a minimal level in later age. On prostate cancer development, PrLZ expression is reactivated, and its expression increases from primary localized tumor to bone metastasis. Overexpression of PrLZ in prostate cancer cells accelerates their growth in vitro and tumor formation in vivo. Conclusion: This work identifies PrLZ as a marker for prostate cancer progression and metastasis, andits pattern of expression is suggestive of a proto-oncogene.

PrLZ expression is associated with the progression of prostate cancer LNCaP cells

“…Androgen-independent, tumorigenic, and bone metastatic C4-2 expressed higher PrLZ levels than that of LNCaP in the LNCaP/C4-2 PCa progression model. Our very recent publication also showed that PrLZ expressed in normal prostate development and in human prostate cancer progression by immunochemistry staining [12]. These data from the above indicated PrLZ has an oncogenic property and contribute to the progression of PCa.…”

Overexpressed oncogenic tumor-self antigens

“…74,75 Expression of TPD52 in cancer TPD52 is an overexpressed tumor self-protein actively involved in transformation, leading to increased proliferation and metastasis. TPD52 overexpression has been demonstrated in several human malignancies including breast, [76][77][78] prostate, [79][80][81] and ovarian carcinomas. 82 Expression microarray and other analyses predict TPD52 overexpression in many other cancers including multiple myeloma, 83,84 Burkitt's lymphoma, 85,86 pancreatic cancer, 87 testicular germ cell tumors, [88][89][90] and melanomas, 91,92 as well as multiple other adult and pediatric cancers.…”

Tumor protein D52 (isoform 3) contributes to prostate cancer cell growth via targeting nuclear factor-κB transactivation in LNCaP cells

“…TPD52 is an oncogene, which is overexpressed in ovarian, breast, and PCas due to gene amplification. 15,18,35 TPD52 gene is located at the chromosome 8q21.1, which is most frequently amplified in PCa. TPD52 expression in different cancer cell types is linked to various cellular functions including proliferation, and its expression is regulated by testosterone in hormone-responsive PCa cells.…”

“…[15][16][17] Recent studies have demonstrated that TPD52 promotes metastasis; its expression increases with advancement of cancer and regulates apoptosis of cancer cells. 18,19 There was ample of interest given to TPD52 as an oncogene, due to its multifaceted functions in various cellular mechanisms and multiple carcinomas. 20,21 It is also proved that TPD52 increases lipid metabolism by facilitating de novo synthesis, exogenous uptake, and intracellular lipid storage.…”

“…17 Overexpression of PrLZ in PCa cells mediates increased tumor formation followed by bone metastasis in vivo. 18,26 Since the specific mechanism through which TPD52 is involved in PCa progression is still under investigation, this study is aimed to understand the effect of TPD52 expression on different cellular signaling pathways in the androgen-responsive PCa cell line LNCaP.…”