STUDIES OF NORMAL AND NEOPLASTIC PROSTATE

前列腺核cAMP非依赖性蛋白激酶(PKs)活性 非组蛋白蛋白(包括核基质蛋白)已经被 由我们建立，以展示早期雄激素调节，这可能是 对雄激素调控基因表达的初始事件至关重要 在前列腺里。我们已经提纯了两个这种不依赖于核阵营的PKs (N1和N2)。这两种酶都能使磷高磷蛋白和酪蛋白磷酸化，但 PK-N_2对非组蛋白的活性更强。类似的酶在 其他系统也牵涉到与以下活动相关的活动的控制 基因作用。我们目前正在提高针对这两种酶的抗体。 对于pk-n2，产生单抗的杂交瘤已经被 发展起来的。特定抗体的可获得性应该有助于 计划中的细胞调控和分子生物学控制研究 这些PKs在雄激素介导的生长控制中的作用 前列腺。与此相关的是我们观察到纯化的前列腺 雄激素受体被一种对雄激素敏感的 核弹头。 我们的目标之一是研究核蛋白和蛋白质 人前列腺染色质的激酶以识别可能的特征 肿瘤性前列腺病与正常前列腺病不同。我们有 完成了对人类正常和良性的一般属性的研究 肥厚性前列腺(BPH)染色质相关蛋白激酶反应。 与对照组相比，BPH染色质的活性没有变化 正常的前列腺染色质，当用磷高磷蛋白或富含赖氨酸的检测时 组蛋白为底物。然而，在以下方面发现显著增长(150%) PK，内源性染色质相关的磷酸化速率， 非组蛋白在良性前列腺增生症染色质中的表达。这个 这一观察到的潜在机制以及对 前列腺癌的染色质正在研究中。(N)

Prostatic nuclear cAMP-independent protein kinases (PKs) active towards non-histone proteins (including nuclear matrix proteins) have been established by us to demonstrate early androgenic modulation which may be critical to the initial events in the androgenic control of gene expression in the prostate. We have purified two such nuclear cAMP-independent PKs (N1 and N2). Both of the enzymes phosphorylated phosvitin and casein, but PK-N2 was more active towards non-histone proteins. Similar enzymes in other systems have been implicated in the control of activities related to gene action. We are currently raising antibodies against the two enzymes. For PK-N2, hybridomas generating monoclonal antibodies have been developed. The availability of specific antibodies should facilitate planned studies of cellular regulation and molecular biological control of these PKs in regard to their role in androgen-mediated growth control in the prostate. Relevant to this is our observation that purified prostatic androgen receptor is phosphorylated by one of the androgen-sensitive nuclear PKs. One of our goals has been to examine the nuclear proteins and protein kinases of human prostatic chromatin to identify features which might differ in the neoplastic prostate as compared with the normal. We have completed a study of the general properties of the human normal and benign hypertrophic prostate (BPH) chromatin-associated protein kinase reactions. There was no change in the activity of the BPH chromatin as compared with the normal prostate chromatin when tested with phosvitin or lysine-rich histone as substrate. However, a marked increase (by 150%) was found in PK, the rate of phosphorylation of endogenous chromatin-associated, non-histone proteins in BPH chromatin as compared with the normal. The underlying mechanism of this observation and also similar studies of the chromatin from prostatic carcinoma are in progress. (N)