Nephew K P, Choi C M, Polek T C, McBride R, Bigsby R M, Khan S A, Husseinzadeh N
Division of Gynecologic Oncology, Department of Anatomy and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Gynecol Oncol. 2000 Mar;76(3):388-96. doi: 10.1006/gyno.1999.5696.
The objective of this study was to evaluate expression of fos and jun proto-oncogenes in benign human uterine tissue compared with malignant uterine tissue.
Forty-two endometrial tissue specimens were obtained at the time of hysterectomy. Tissue samples from different phases of the menstrual cycle and from postmenopausal patients were stained using immunohistochemical methods to detect Fos and Jun proteins, estrogen and progesterone receptor status, and Ki67 (detects a nuclear antigen associated with proliferating cells). Tissue was examined microscopically for nuclear staining in endometrial epithelium and stroma. The endometrium was based on the patient's last menstrual period, pathologic dating, and proliferative versus nonproliferative status as determined by Ki67. Benign and malignant specimens were subjected to Northern blot analysis to evaluate levels of expression of c-fos, c-jun, and jun-B mRNA. The pattern of c-fos mRNA expression in malignant samples was further evaluated using in situ hybridization.
In proliferative, secretory, postmenopausal, and progesterone-influenced, uterine specimens immunohistochemically stained and examined, the endometrial and stromal nuclei stained for both Fos and Jun in varying intensities. However, no pattern was found in the variation of intensity according to the phase of the endometrium. Similarly, in malignant and benign endometrial tissue examined by Northern blot and in situ hybridization analyses, expression of proto-oncogene mRNAs was readily detectable, but no statistical correlation between type of tissue examined, grade of adenocarcinoma, and stage of endometrial cancer was found in this study.
In rodent models, control of uterine cell proliferation is related to change in expression of fos and jun proto-oncogenes. Our results indicate that hormonal control is likely to be different in human endometrium and probably involves genes other than the proto-oncogenes under study. Expression of Fos and Jun do not correlate with endometrial cancer stage and grade.
本研究的目的是评估原癌基因fos和jun在良性人子宫组织与恶性子宫组织中的表达情况。
在子宫切除时获取42份子宫内膜组织标本。采用免疫组织化学方法对来自月经周期不同阶段和绝经后患者的组织样本进行染色，以检测Fos和Jun蛋白、雌激素和孕激素受体状态以及Ki67（检测与增殖细胞相关的核抗原）。在显微镜下检查组织，观察子宫内膜上皮和基质中的核染色情况。根据患者的末次月经、病理分期以及Ki67确定的增殖与非增殖状态对子宫内膜进行评估。对良性和恶性标本进行Northern印迹分析，以评估c-fos、c-jun和jun-B mRNA的表达水平。使用原位杂交进一步评估恶性样本中c-fos mRNA的表达模式。
在对增殖期、分泌期、绝经后以及受孕激素影响的子宫标本进行免疫组织化学染色和检查时，子宫内膜和基质细胞核均以不同强度对Fos和Jun染色。然而，未发现强度变化与子宫内膜阶段之间存在特定模式。同样，在通过Northern印迹和原位杂交分析检查的恶性和良性子宫内膜组织中，原癌基因mRNA的表达易于检测到，但在本研究中未发现所检查的组织类型、腺癌分级与子宫内膜癌分期之间存在统计学相关性。
在啮齿动物模型中，子宫细胞增殖的控制与原癌基因fos和jun表达的变化有关。我们的结果表明，人类子宫内膜中的激素控制可能不同，可能涉及除所研究的原癌基因之外的其他基因。Fos和Jun的表达与子宫内膜癌的分期和分级无关。
