Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
PLoS One. 2013 Aug 29;8(8):e72849. doi: 10.1371/journal.pone.0072849. eCollection 2013.
CD44 marks stem cell-like cells in a number of tumour types, including colorectal cancer (CRC), while aberrant CD44 expression conveys increased tumourigenic, invasive, and metastatic potential. Previous data indicate that CD44 is a direct target of p53-mediated transcriptional repression in breast cancer. Since inactivating p53 mutations are frequent genetic events in CRC these could unleash expression of CD44. In the present study, we therefore explored the relation between p53 mutational status and CD44 expression in a cohort of 90 localized primary CRCs and studied the effect of radiation-induced p53 activation on CD44 expression. Interestingly, we observed that, in contrast to breast cancer, loss of function p53 mutations were not associated with elevated CD44 expression in colon cancer. Moreover, DNA-damage induced p53 activation did not result in repression of CD44 expression, neither in colon cancer cells nor in normal intestinal epithelial cells. Our data demonstrate that CD44 expression in normal and malignant intestinal epithelial cells is not regulated by p53, implying that regulation of this potentially important therapeutic target is tissue and cancer-type specific.
CD44 标记了多种肿瘤类型中的干细胞样细胞，包括结直肠癌（CRC），而异常的 CD44 表达赋予了肿瘤更强的致瘤性、侵袭性和转移性。先前的数据表明，CD44 是乳腺癌中 p53 介导的转录抑制的直接靶标。由于 CRC 中 p53 失活突变是常见的遗传事件，这可能会释放 CD44 的表达。因此，在本研究中，我们在 90 例局部原发性 CRC 患者中探讨了 p53 突变状态与 CD44 表达之间的关系，并研究了辐射诱导的 p53 激活对 CD44 表达的影响。有趣的是，我们观察到与乳腺癌相反，在结肠癌中，功能丧失 p53 突变与 CD44 表达的升高无关。此外，DNA 损伤诱导的 p53 激活不会导致 CD44 表达的抑制，无论是在结肠癌细胞还是在正常肠上皮细胞中均如此。我们的数据表明，正常和恶性肠上皮细胞中的 CD44 表达不受 p53 调控，这意味着对这个潜在重要治疗靶点的调控具有组织和癌症类型特异性。
