Einspahr Janine G, Krouse Robert S, Yochim Ji Min, Danenberg Peter V, Danenberg Kathleen D, Bhattacharyya Achyut K, Martínez María E, Alberts David S
Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
Cancer Res. 2003 Jul 15;63(14):3891-3.
The cyclooxygenase (COX) pathway is important in colorectal carcinogenesis with the majority of cancers overexpressing COX-2; however, the role of COX-2 in the development of colorectal adenomas is less well defined. Accordingly, we analyzed 108 colorectal adenomas for COX-1 and COX-2 transcription in archival formalin-fixed, paraffin-embedded tissue using by real-time PCR and normalized to beta-actin. Neither COX-1 nor COX-2 mRNA expression differed with regard to age or gender of the subject. COX-2 mRNA expression was significantly higher in distal adenomas (2.2 +/- 1.9) compared with proximal (0.7 +/- 0.5) adenomas (P < 0.0001) and in larger (>/=7 mm) compared with smaller (<7 mm) adenomas (2.3 +/- 2.2 and 1.7 +/- 1.3, respectively, P = 0.04). COX-2 expression did not differ significantly in tubular compared with tubulovillous adenomas, although there appeared to be a trend toward higher COX-2 expression in tubulovillous adenomas with increasing villous content. Additionally, there was not a significant difference in either COX-1 or COX-2 based on the degree of dysplasia Therefore, if COX-2 inhibitors work through a COX-2 mechanism, these agents may have differential effects on colorectal adenomas that are distal and larger.
环氧化酶（COX）途径在结直肠癌发生过程中具有重要作用，大多数癌症中COX-2过表达；然而，COX-2在结直肠腺瘤发生中的作用尚不清楚。因此，我们使用实时聚合酶链反应（PCR）并以β-肌动蛋白作为内参，分析了108例存档的福尔马林固定、石蜡包埋组织中的结直肠腺瘤的COX-1和COX-2转录情况。COX-1和COX-2的mRNA表达在受试者的年龄或性别方面均无差异。与近端腺瘤（0.7±0.5）相比，远端腺瘤（2.2±1.9）中COX-2的mRNA表达显著更高（P<0.0001）；与较小（<7mm）的腺瘤（分别为2.3±2.2和1.7±1.3）相比，较大（≥7mm）腺瘤中COX-2的mRNA表达也显著更高（P=0.04）。与管状绒毛状腺瘤相比，管状腺瘤中COX-2的表达无显著差异，尽管随着绒毛成分增加，管状绒毛状腺瘤中COX-2表达似乎有升高趋势。此外，根据发育异常程度，COX-1或COX-2的表达均无显著差异。因此，如果COX-2抑制剂通过COX-2机制发挥作用，这些药物可能对远端和较大的结直肠腺瘤产生不同的影响。
