Thioesterase II, the key enzyme which regulates the production of medium-chain fatty acids by the mammary fatty acid synthetase, is expressed specifically in epithelial cells of the rat mammary gland, regardless of their state of differentiation, and we consider the enzyme to be a reliable marker for this cell type. The objective of this study was to determine whether this enzyme is expressed universally in tumors originating from rat mammary epithelial cells and whether it might be shed into the serum of host animals. Immunoreactive thioesterase II was detected in all of the epithelial derived mammary tumors tested, being highest in tumors that exhibited obvious epithelial morphology. Two of the tumors, R3230AC and DMBA 1, were transplanted into Fischer 344 rats and the levels of thioesterase II in the tumor and serum were monitored by enzyme immunoassay. Thioesterase II content of the transplanted tumors fell to, and remained at, a low level during the first week following transplantation. During this period the transplanted tumor established a new network of blood vessels; no thioesterase II was detectable in the serum. Subsequently, thioesterase II levels in the tumors returned to the values observed before transplantation and thioesterase II was detectable in the serum. Of 51 rats transplanted with the R3230AC tumor, 37 showed elevated serum thioesterase II levels; of 40 transplanted with the DMBA 1 tumor, 35 showed elevated serum thioesterase II. Furthermore, there was a statistically significant correlation between serum thioesterase II and tumor burden in both tumor model systems. The identity of the serum antigen reacting with anti-thioesterase II antibodies was confirmed, by Western immunoblotting, to be full-length thioesterase II polypeptide. Parallel studies with fatty acid synthetase, an enzyme with an ubiquitous tissue distribution, indicated as expected that serum levels of this enzyme were unlikely to provide a reliable index of mammary tumor status.

These results indicate that thioesterase II may be a useful serum marker for mammary cancer.

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Supported by a joint venture of Children's Hospital Medical Center and Hambrecht & Quist.

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