Differential expression of matrilysin and cyclooxygenase‐2 in intestinal and colorectal neoplasms
Differential expression of matrilysin and cyclooxygenase‐2 in intestinal and colorectal neoplasms
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Matrilysin 和 cyclooxygenase-2 在肠道和结直肠肿瘤中的差异表达
DOI：
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发表时间：
1999
影响因子：
4.6
通讯作者：
L. Matrisian
中科院分区：
文献类型：
--
作者：
R. Shattuck;L. Lamps;K. Heppner Goss;R. Dubois;L. Matrisian
基质金属蛋白酶基质溶解素和前列腺素H合酶环氧化酶-2（考克斯-2）被认为在结直肠癌发生中起关键作用。这些酶在85-90%的人类结直肠癌中过表达。此外，携带腺瘤性结肠息肉病生殖系突变的小鼠（也是基质溶素或考克斯-2的无效合子）显示肿瘤多样性显著降低。为了确定基质溶解素和考克斯-2之间是否存在直接联系，在两种肠道癌发生小鼠模型和人结肠直肠肿瘤样品中表征了它们的表达。基质溶解素和考克斯-2的表达在小鼠模型和人结直肠癌中均增加;然而，免疫组织化学和原位杂交表明它们在肿瘤中的定位是不同的。在小鼠模型中，考克斯-2在浅表基质中表达，而基质溶解素表达仅局限于肿瘤上皮。相反，在人类结直肠癌中，考克斯-2和基质溶解素均在肿瘤上皮中表达。尽管超过80%的标本同时表达基质溶解素和考克斯-2，但基质溶解素和考克斯-2表达的水平和定位不同。考克斯-2表达在分化良好的区域最强，基质溶解素免疫染色在肿瘤的发育不良和侵袭性区域最强。这些结果表明，这两种重要的结直肠肿瘤发生调节剂差异表达，并暗示利用选择性考克斯-2和基质溶解素抑制剂的联合治疗可改善治疗益处。摩尔巨蟹座24：177-187，1999.© 1999 Wiley利斯公司
Both the matrix metalloproteinase matrilysin and the prostaglandin H synthase cyclooxygenase‐2 (Cox‐2), are thought to play key roles in colorectal carcinogenesis. These enzymes are overexpressed in 85–90% of human colorectal cancers. Furthermore, mice carrying an adenomatous polyposis coli germline mutation that are also nullizygous for either matrilysin or Cox‐2 display a significant reduction in tumor multiplicity. To determine if there is a direct link between matrilysin and Cox‐2, their expression was characterized in two mouse models of intestinal carcinogenesis and in human colorectal tumor samples. Both matrilysin and Cox‐2 expression was increased in the mouse models and in the human colorectal cancers; however, immunohistochemistry and in situ hybridization indicated that their localization within the tumors was different. In the mouse models, Cox‐2 was expressed in the superficial stroma, whereas matrilysin expression was localized exclusively to the neoplastic epithelium. In contrast, in human colorectal cancers, both Cox‐2 and matrilysin were expressed in the neoplastic epithelium. Although over 80% of the specimens expressed both matrilysin and Cox‐2, the levels and localization of matrilysin and Cox‐2 expression were distinct. Cox‐2 expression was strongest in well‐differentiated areas, and matrilysin immunostaining was strongest in the more dysplastic and invasive regions of the tumor. These results indicate that these two important modulators of colorectal tumorigenesis are differentially expressed and imply that the therapeutic benefit may be improved by combination therapy utilizing selective Cox‐2 and matrilysin inhibitors. Mol. Carcinog. 24:177–187, 1999. © 1999 Wiley‐Liss, Inc.
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影响因子：
29.4
作者：
Williams, CS;Luongo, C;DuBois, RN
通讯作者：
DuBois, RN
影响因子：
56.9
作者：
NISHISHO, I;NAKAMURA, Y;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.1073/pnas.94.4.1402
发表时间：
1997-02-18
影响因子：
11.1
作者：
Wilson, CL;Heppner, KJ;Matrisian, LM
通讯作者：
Matrisian, LM
影响因子：
4.7
作者：
BeazerBarclay, Y;Levy, DB;Kinzler, KW
通讯作者：
Kinzler, KW
影响因子：
56.9
作者：
MOSER, AR;PITOT, HC;DOVE, WF
通讯作者：
DOVE, WF