Etk͞Bmx is the newest member of Btk tyrosine kinase family that contains a pleckstrin homology domain, an src homology 3 domain, an src homology 2 domain, and a catalytic domain. Unlike other members of the Btk family kinases, which are mostly hemopoietic cell-specific, Etk͞Bmx is preferentially expressed in epithelial and endothelial cells. We first identified this kinase in prostate cancer

(20). Fifty micrograms of total cellular RNA was used for reverse

The insulin-like growth factor (IGF) binding proteins (IGFBPs) are important modulators of IGF action in many tissues including human prostate. IGFBPs and the androgen receptor (AR) are expressed in CWR22, an androgen-dependent epithelial cell human CaP xenograft that retains biological characteristics of human CaPs, including regression following androgen withdrawal and recurrent growth of AR-containing cells in the absence of testicular androgens beginning several months after castration. Northern blot and in situ hybridization analyses demonstrated that IGFBP-5 is androgen-regulated in CWR22. IGFBP-5 messenger RNA (mRNA) decreased by 90% following castration of tumor-bearing mice compared with noncastrate androgen-stimulated mice. Testosterone treatment of CWR22 tumor-bearing mice 6 or 12 days after castration increased IGFBP-5 mRNA 10- to 12-fold. Levels of other IGFBP mRNAs did not change following androgen withdrawal and replacement. IGFBP-5 protein in tumor extracts bound 125I-labeled IGF-I in ligand blot assays and the amounts of IGFBP-5 measured by immunoblotting paralleled the levels of IGFBP-5 mRNA. Androgen-induced expression of IGFBP-5 was at a maximum level within 24 h after testosterone replacement, whereas the major increase in cell proliferation as measured by Ki-67 immunostaining occurred between 24-48 h. This time course suggested IGFBP-5 may be a mediator of androgen-induced growth of CWR22. In tumors that recurred several months following castration, IGFBP-5 mRNA and protein increased to levels that approached those in androgen-stimulated CWR22 tumors from noncastrate mice. IGFBP-5 immunohistochemical staining of prostate tissue specimens from patients was stronger in androgen-dependent and androgen-independent CaP than in areas of intraepithelial neoplasia (PIN) or benign prostatic hyperplasia (BPH). IGFBP-5 mRNA in these specimens was localized predominantly to stromal cells and IGFBP-5 protein to epithelial cell membranes.

C-ret proto-oncogene encodes a protein in the tyrosine kinase (TK) family of transmembrane receptors for growth factors. C-ret expression has been identified in normal tissues and tumors of neural crest origin such as inherited MEN (multiple endocrine neoplasia) syndromes, particularly medullary thyroid cancers where there are confirmed germ-line mutations. Gene rearrangement has been observed in papillary thyroid carcinomas (PTC) and has been shown to have cytoplasmic localization of the altered gene product. C-ret proto-oncogene product is also necessary for the normal development of the peripheral nervous system, enteric nervous system and the kidney. A recent profile of the TK receptors in prostate cancer (PCA) identified c-ret protein in prostate cancer tissue and xenograft derived from human PCA. This study is the first to report the immunohistochemical (IH) evaluation of c-ret in human prostatic tissue.Thirty radical prostatectomy specimens for PCA were formalin-fixed, sectioned at 5mm and paraffin-embedded.