Royuela M, de Miguel M P, Ruiz A, Fraile B, Arenas M I, Romo E, Paniagua R
Department of Cell Biology and Genetics, University of Alcalá, E-28871 Alcalá de Henares, Madrid, Spain.
Eur Cytokine Netw. 2000 Mar;11(1):119-27.
The therapeutic potential of IFN-gamma in prostatic cancer has been documented in several reports, although no immunohistochemical studies of this factor and its receptors in the prostate have been reported. The aim of the present study was to investigate the expression of IFN-gamma and its receptor components (IFN-gamma-Ralpha and IFN-gamma-Rbeta) in normal prostate, benign prostatic hyperplasia (BPH) and prostatic cancer (PC), as well as the possible relationship between this factor and the products of the p53 gene (the wild and mutant forms) and the oncogene c-myc, by means of immunochemical techniques (Western blot, ELISA, and quantification of immunostaining in histological sections). In normal prostate, IFN-gamma and its two receptors were expressed in the basal cells of the epithelium and some stromal cells. In BPH specimens, immunostaining of basal epithelial cells was significantly increased for IFN-gamma and its a receptor, whereas stromal cell immunostaining was significantly increased for IFN-gamma and its b receptor. In addition, columnar epithelial cells immunostained for IFNbeta-Rbeta. PC specimens differed from BPH specimens in the significantly increased immunostaining of epithelial cells for IFN-gamma and its two receptors, and the immunostaining of columnar epithelial cells for IFN-gamma-Ralpha. Immunodetection of wild-p53 was weak and limited to some stromal cells in the three types of specimens. Immunostainings for both mutant-p53 and c-myc were negative in normal prostate, and positive in the epithelium and stromal cells of both BPH and PC specimens. Immunostaining intensity in PC was significantly higher than in BPH. These observations suggest that the expression of both mutant-p53 and c-myc, together with other factors, might be involved in the development of prostatic hyperplasia and neoplasia, while the increased expression of IFN-gamma and its receptors could be regarded as an attempt, although insufficient, to inhibit the uncontrolled cell proliferation.
尽管尚无关于该因子及其受体在前列腺中的免疫组织化学研究报道，但已有数篇报告证实了γ干扰素在前列腺癌中的治疗潜力。本研究旨在通过免疫化学技术（蛋白质印迹法、酶联免疫吸附测定法以及组织学切片免疫染色定量分析），研究γ干扰素及其受体成分（γ干扰素受体α和γ干扰素受体β）在正常前列腺、良性前列腺增生（BPH）和前列腺癌（PC）中的表达情况，以及该因子与p53基因产物（野生型和突变型）和癌基因c-myc之间的可能关系。在正常前列腺中，γ干扰素及其两种受体在上皮基底细胞和一些基质细胞中表达。在BPH标本中，基底上皮细胞中γ干扰素及其α受体的免疫染色显著增加，而基质细胞中γ干扰素及其β受体的免疫染色显著增加。此外，柱状上皮细胞对γ干扰素受体β呈免疫染色阳性。PC标本与BPH标本的不同之处在于，上皮细胞中γ干扰素及其两种受体的免疫染色显著增加，以及柱状上皮细胞对γ干扰素受体α的免疫染色增加。野生型p53的免疫检测较弱，且仅限于三种标本类型中的一些基质细胞。在正常前列腺中，突变型p53和c-myc的免疫染色均为阴性，而在BPH和PC标本的上皮细胞和基质细胞中均为阳性。PC中的免疫染色强度显著高于BPH。这些观察结果表明，突变型p53和c-myc的表达以及其他因素可能参与了前列腺增生和肿瘤形成的发展，而γ干扰素及其受体表达的增加可被视为一种抑制细胞不受控制增殖的尝试，尽管并不充分。
