转录调节因子Ets-1在大鼠血管平滑肌细胞增殖与凋亡中的作用

目的： 研究转录调节因子Ets-1对大鼠血管平滑肌细胞增殖与凋亡的影响及其可能的机制。 方法： 用定量细胞DNA片段的方法观察大鼠血管平滑肌细胞增殖与凋亡。用Western印迹法检测磷酸化视网膜母细胞瘤（RB-P）蛋白表达。 结果： Ets-1抑制大鼠血管平滑肌细胞凋亡。反义P21WAF1/CIP1能够阻断Ets-1的抗凋亡作用，并抑制Ets-1诱导的平滑肌细胞增殖。Ets-1能够上调RB-P蛋白表达，反义P21WAF1/CIP1可以阻断Ets-1诱导的RB-P蛋白表达。 结论： 在大鼠血管平滑肌细胞中，Ets-1通过P21WAF1/CIP1旁路发挥抑制凋亡和促进增殖作用。     

Ets-1 deficiency leads to altered B cell differentiation, hyperresponsiveness to TLR9 and autoimmune disease

It has been shown that mice with a targeted mutation in the Ets-1 gene exhibit increased B cell terminal differentiation to IgM-secreting plasma cells. Here, we show that mice, formerly described to lack Ets-1 protein, actually express low levels of an internally deleted Ets-1 protein. Mice harboring this Ets-1 hypomorphic allele possess very few marginal zone B cells and have increased expression of activation markers on follicular B cells. Adoptive transfer experiments indicate that this activated phenotype can be reversed upon transfer of Ets-1-deficient B cells to a wild-type host, suggesting a role for B cell-extrinsic factors in regulating the activated state. Supporting this observation, the reverse transfer experiment of wild-type B cells into an Ets-1-deficient host resulted in increased expression of activation markers on the transferred B cells. However, there are also cell-intrinsic changes in Ets-1-deficient B cells as demonstrated by their increased differentiation to plasma cells in vitro in response to stimulation with cytosine-phosphate-guanine DNA sequence-containing oligodeoxynucleotide [CpG DNA, a Toll-like receptor (TLR) 9 ligand]. Consistent with the activated phenotype and increased terminal differentiation of Ets-1-deficient B cells, Ets-1 mutant mice develop autoimmune disease. Hence, our studies establish Ets-1 as an important regulator of peripheral B cell differentiation and B cell responses to TLR9 activation.     

Overexpression of Ets-1 proto-oncogene in latent and clinical prostatic carcinomas

AIMS: The high incidence of clinically diagnosed prostatic cancer is exceeded by the frequency of tumours detected at autopsy. The Ets-1 proto-oncogene is expressed by a variety of malignant and normal tissues. Therefore, in this study, expression of Ets-1 protein was investigated in 'latent' prostatic cancer detected at autopsy, compared with benign prostatic hyperplasia, normal prostatic tissues and clinical prostatic cancer. METHODS AND RESULTS: Using immunohistochemistry, we analysed Ets-1 expression in 95 prostatic specimens including 19 cases of latent prostatic carcinoma (LPC) and 55 cases of clinical prostatic carcinoma (CPC), 11 cases of benign prostatic hyperplasia (BPH) and 10 cases of normal prostate (NP). Differences in the incidence of LPC and CPC suggest different courses for the biological progression of prostatic cancer. There was a significant difference in the degree of Ets-1 expression in CPC and LPC (P < 0.05). Ets-1 was not expressed in BPH and NP, but in malignant cases (57 of 74; 77.0%) commonly demonstrated immunoreactivity in the tumour cells. In our study the expression of Ets-1 between benign and malignant, and well, moderately and poorly differentiated adenocarcinomas of prostatic cancer showed significant differences. The presence of Ets-1 mRNA was confirmed by in-situ hybridization in human prostatic tissues. CONCLUSION: Our results suggest that Ets-1 might play an important role in carcinogenesis and/or the progression of human prostatic carcinomas.