A gene designated H-MAM has been identified, cloned, and sequenced from the human mammary carcinoma cell line MCF-7. This gene was detected based upon its ability to transform NIH3T3 cells in the DNA transfection assay. Our original observation was that a common gene was activated in this line and in six mouse mammary tumors, based upon sensitivity of the gene to inactivation by a panel of restriction endonucleases. The isolated, intronless gene contains an unconventional putative promotor region which is GC rich and contains SP1 binding sites, similar to that observed for the neu oncogene and for the EGF receptor. Two conventional polyadenylation signals are present. The putative protein encoded by H-MAM is 11.8 Kd and has structural features in common with other small, growth-related peptide hormones. One n-linked glycosylation site is present in this 107AA protein. Because of putative promotor region similarities to peptide hormone receptors and because of structural similarity to other small peptide hormone, we hypothesize that H-MAM may function as a small growth- related peptide hormone. Further characterization of H-MAM will include definition of the activational region by comparison with the non-transforming allele; local localization of the protein; definition of the expressional range in breast and non-breast related tissue; determination of hormonal influence on protein expression, and definition of the activational range in other human breast tumors. We believe that definition of the role of this protein in normal and abnormal growth states may provide new insights applicable to the treatment of human breast cancer.
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