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The ADAMs are multidomain proteins possessing both adhesion and MMP-like domains. Currently, 40 different ADAMs are known to exist. One of the most widely studied members of this family is ADAM-17 or TACE (tumor necrosis factor α converting enzyme). TACE is potentially important in cancer as it is responsible for the processing of a number of growth factors and cytokines that are causally involved in cancer formation and progression (eg, TNF-alpha, TGF-alpha, amphiregulin and HB-EGF). The aim of this investigation was to study the expression and ultimately explore a potential clinical value for TACE in breast cancer. Using RT-PCR, TACE mRNA was detected in 14/34 (41.2%) normal breast tissues, 8/23 (34.8%) fibroadenomas, 73/139 (52.5%) primary breast carcinomas and 9/14 (64.3%) axillary nodal metastases. Levels of TACE mRNA were significantly higher in primary breast carcinoma compared to fibroadenomas (Mann Whitney U test: p = 0.028). In a cohort of 17 matched malignant and normal breast tissues, levels of TACE mRNA were significantly higher in the breast carcinomas compared to the matched normal breast tissue (Mann Whitney U test: p = 0.026). Using Western blotting, TACE protein was found to exist in two main forms with molecular weights of approximately 130 kDa and 110 kDa. Levels of both the 130 kDa and 110 kDa forms were significantly higher in primary breast carcinomas as compared to normal breast tissues (Mann Whitney U test: p = 0.005 and 0.0003, respectively). Furthermore, levels of the 110 kDa form were also significantly higher in primary breast carcinomas as compared to fibroadenomas (Mann Whitney U test: p = 0.01). TACE 110 kDa was expressed more frequently in lymph node-positive carcinomas than lymph-node negative specimens (Chi square: p = 0.03). However, TACE protein expression was independent of tumour size, tumour grade, steroid receptor status and histology. We conclude that: (a) TACE mRNA levels are significantly higher in primary breast carcinomas as compared to normal breast tissues and fibroadenomas, (b) the 130 kDa protein may represent the proform of TACE, with the 110 kDa band corresponding to the active form and (c) TACE protein levels were found to be significantly higher in primary breast carcinomas as compared to normal breast tissue and fibroadenomas. These findings suggest that TACE may be involved in breast tumorigenesis.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]