In contrast, intense survivin immunoreactivity was found in Spermine interphase nuclei and in the cytosol of most transformed cells within PIN lesion and invasive cancers in TRAMP mice.Heterogeneity in the percentage of transformed cells expressing survivin, however, resulted in some cases scoring as negative, where at least immunopositivity was set as the threshold. The intensity of XIAPMIAP immunostaining also increased during malignant transformation, although more aggressive tumors that had infiltrated seminal vesicles rarely contained high levels of this protein.The specificity of these immunostaining results was confirmed by control stainings performed using either preimmune serum or immune antisera that had been preabsorbed with the relevant immunogens. Immunoblot analysis at least partially corroborated these findings.Expression of M IAP, and XIAPMIAP was detected in every tumor specimen evaluated were readily documented by immunoblotting for all tumor specimens evaluated.Cancerassociated increases in MIAP, XIAPMIAP, and survivinMIAP were more heterogeneous, as measured by comparisons of normal and tumor tissue by immunoblotting, possibly because of admixture of normal and malignant cells.Thus, we conclude that tumorassociated overexpression of several IAP family proteins occurs during prostate cancer development in TRAMP mice.Deregulation of apoptosis contributes to tumor initiation, progression to the androgeninsensitive state, and metastasis.IAP family proteins represent critical regulators of apoptosis that serve as endogenous inhibitors of caspase family cell death proteases. Our immunohistochemical analysis demonstrates for the first time that alterations in the expression of several IAP family proteins occur commonly and often simultaneously in prostate cancers.Previously, survivin was reported to be aberrantly overexpressed in most cancers, including prostate, lung, colon, breast, pancreatic, and gastric cancer and others. However, little is known about the expression of other members of the IAP family in cancers.Higher levels of XIAP protein have been correlated with shorter remission duration after chemotherapy and shorter survival in patients with acute myelogenous leukemia. Thus, when combined with these prior reports, our data provide additional evidence that pathological elevations in the expression of antiapoptotic IAP family proteins represent a common event in many types of cancer.Not only were elevations in IAP family proteins seen in archival human prostate cancer specimens, but we also observed increases in the levels of cIAPMIAP, cIAPMIAP, XIAPMIAP, and survivinMIAP during disease progression in a transgenic mouse model of prostate cancer.Upregulation of IAP expression concomitant with the emergence of PIN implicates a role of these proteins in the early stages of the pathogenesis of prostate cancer and emphasizes the utility of TRAMP for identifying molecular changes in early disease.This finding suggests that overexpression of IAP family proteins is a general concomitant of transformation of prostate epithelium and cystine reinforces the idea that multiple IAP family members become dysregulated in their expression during the pathogenesis of malignancy in the prostate gland.It remains to be seen whether the simultaneous overexpression of several IAP family proteins reflects a commonality in the mechanisms controlling the levels of IAP family proteins in cells versus the possibility that multiple independent signaling pathways that control individual IAP family members become simultaneously deregulated in these neoplasms.Based on the data provided here, we cannot conclude whether differences in the expression of one or more IAP family proteins are of prognostic significance for men with prostate cancer.