We have previously reported on cloning of the human gene encoding Bcl-2/adenovirus E1B 19 kDa-interacting protein 3-like protein (Bnip3L) and its growth inhibitory eect on cancer cells. Here we show that Bnip3L contains a motif similar to the BH3 domain which is conserved in Bcl-2 family proteins as well as containing a membrane-anchoring domain, and that Bnip3L interacts with Bcl-2 and Bcl-x L . Immuno¯uorescence microscopy revealed that Bnip3L was localized in the mitochondria, when in the presence of the membrane-anchoring domain. Transient expression of Bnip3L induced apoptosis of Rat-1 and HeLa cells and mutational analysis revealed that the BH3 domain and the membrane-anchoring domain were required for Bnip3L to induce cell death. Addition of recombinant Bnip3L to isolated mitochondria induced membrane potential loss and cytochrome c release both of which have been suggested to be prerequisite for apoptotic cell death. These results suggest that Bnip3L is one of the BH3-containing proapoptotic proteins and that it targets the mitochondria when inducing apoptosis.

Recent studies demonstrated that a single guanine insertion polymorphism in a matrix metalloprotease‐1 promoter created an Ets binding site and affected the elevation of the transcriptional level of matrix metalloproteinase‐1 (MMP‐1). Furthermore, in tumor cell lines derived from melanoma and breast cancer, the incidence of the 2G/2G genotype was significantly higher than that in the normal population. To evaluate the contribution of this polymorphism in endometrial carcinomas, we genotyped 100 endometrial carcinomas and then analyzed immunoexpression of MMP‐1 in these carcinomas. We found that endometrial carcinoma patients showed a significantly higher rate of 1G/2G or 2G/2G genotype than control individuals, and that tumors containing the 2G allele(a) expressed MMP‐1 protein more frequently than those with 1G/1G genotype. Therefore, the single nucleotide polymorphism at the MMP‐1 promoter affected the expression level of the MMP‐1 protein, which may result in the association with more aggressive character in endometrial carcinoma. Our result suggests that the presence of 2G polymorphism at the MMP‐1 promoter may be one of the risk factors for the development and/or progression of endometrial carcinoma.

VNTR (variable number of tandem repeat) markers, also called single-copy minisatellites, were originally isolated from human DNA as highly informative restriction fragment length polymorphisms for mapping purposes. Evidence has lately emerged that some VNTR sequences play significant roles in the regulation of transcription, and that some may also influence the translational efficiency or stability of mRNA, or modify the activity of proteins by altering their structure. Some apparent associations of VNTR sequences with personality traits or with susceptibility to diseases have strengthened the likelihood that these tandemly-repeated genomic elements are of physiological and biological importance. In this review, we summarize recent progress in efforts to clarify mechanisms involving VNTR sequences.

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