The transcription factor DEC1 (stra13, SHARP2) is associated with the hypoxic response and high tumour grade in human breast cancers.
The transcription factor DEC1 (stra13, SHARP2) is associated with the hypoxic response and high tumour grade in human breast cancers.
复制标题
DOI：
10.1038/sj.bjc.6602059
复制
发表时间：
2004-08-31
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
DEC 1，也称为SHARP-2或Stra 13，在小鼠胚胎发育、增殖、凋亡和细胞分化中起重要作用。最近在人肾癌细胞系RCC 4的cDNA微阵列研究中鉴定出DEC 1是低氧诱导的，通过低氧诱导因子（HIF）-1α和通过HIF-1α调节，能够阻断脂肪细胞分化。然而，其在人乳腺癌中的分布和在缺氧和分化中的作用尚不清楚。因此，我们研究的模式和DEC 1的表达水平，在正常的，原位和浸润性乳腺癌的整个组织切片中使用免疫组化，并相关的DEC 1的表达水平和临床病理因素和缺氧肿瘤标志物在253个浸润性癌的组织芯片。我们观察到在从正常癌到原位癌和侵袭性癌的进展过程中DEC 1表达增加。表达不限于肿瘤细胞元素，但也观察到内皮细胞，成纤维细胞和炎症细胞。DEC 1与肿瘤分级呈正相关（P=0.01），HIF-1α（P=0.04）和缺氧调节基因血管生成素（P<0.0001），但未观察到与患者年龄的显著相关性（P=0.15）、淋巴结状态（P=0.8）、肿瘤大小（P=0.3）、雌激素受体（P=0.45）、表皮生长因子受体（P=0.27）或Chalkley血管计数（P=0.45）。无复发生存率（P=0.84）或总生存率（P=0.78）无差异。这些发现表明，DEC 1在浸润性乳腺癌的进展中起着重要作用，它可能提供了一种缺氧阻断肿瘤分化的机制，并可能导致更具侵袭性的表型。逆转这种表型可能会改变个体肿瘤的生物学行为。
DEC1, also known as SHARP-2 or Stra13, plays important roles in embryonic development, proliferation, apoptosis and cell differentiation in the mouse. DEC1 was recently identified as hypoxically induced in cDNA microarray studies of the human renal carcinoma cell line RCC4, to be regulated through hypoxia-inducible factor (HIF)-1α and via HIF-1α, able to block adipocyte differentiation. Nevertheless, its distribution and role in hypoxia and differentiation in human breast cancer are unknown. We therefore examined the pattern and level of expression of DEC1 using immunohistochemistry in whole tissue sections in normal, in situ and invasive breast carcinomas, and correlated the level of expression of DEC1 and clinicopathological factors and hypoxic tumour markers in 253 invasive carcinomas on tissue microarrays. We observed an increase in DEC1 expression during progression from normal to in situ and invasive carcinoma. Expression was not restricted to the tumour cell element but was also observed in endothelial, fibroblasts and inflammatory cells. There was a significant positive correlation between DEC1 and tumour grade (P=0.01), HIF-1α (P=0.04) and the hypoxically regulated gene angiogenin (P<0.0001), but no significant associations were observed with patient age (P=0.15), lymph node status (P=0.8), tumour size (P=0.3), oestrogen receptor (P=0.45), epidermal growth factor receptor (P=0.27) or Chalkley vessel count (P=0.45). There was no difference in relapse-free (P=0.84) or overall (P=0.78) survival. These findings suggest that DEC1 plays an important role in the progression to invasive breast cancer and that it may provide a mechanism by which hypoxia blocks tumour differentiation, and may contribute to a more aggressive phenotype. Reversing this phenotype may alter the biological behaviour of individual tumours.
登录
查看更多内容
影响因子：
4.8
作者：
Li, YX;Xie, MX;Yan, BF
通讯作者：
Yan, BF
影响因子：
10.5
作者：
Boudjelal, M;Taneja, R;Chambon, P
通讯作者：
Chambon, P
DOI：
10.1006/bbrc.2000.4133
发表时间：
2001-01-12
影响因子：
3.1
作者：
Fujimoto, K;Shen, M;Kato, Y
通讯作者：
Kato, Y
影响因子：
3.5
作者：
Rossner, MJ;Dorr, J;Nave, KA
通讯作者：
Nave, KA
影响因子：
5.6
作者：
Lennon, DP;Edmison, JM;Caplan, AI
通讯作者：
Caplan, AI