| Breast cancer has become the leading cause of cancer death in women. The epidemiological studies showed that the incidence and mortality rate of breast cancer ranked the top among the female cancer. In spite of many routine methods including Surgical treatment for breast cancer, the recurrence rate were still up to 5%-30% and these methods were no effective for patients with metastasis. Since the identification and cloning of BRCA1 and BRCA2, much attention has been paid to tumor suppressor gene investigation, which is significant both in elucidating the mechanism of transformation and in early diagnosis and gene therapy for breast cancer.In the past years, more tumor suppressor genes were identified to be involved in breast cancer. A promising group of potentially valuable anti-tumor agents are endogenous polypeptide growth inhibitors, which function during normal tissue modeling. In case of mammary gland, several endogenous factors with growth inhibitory or differentiation inducing activity on mammary epithelial cells have been characterized, such as transforming growth factor beta (TGF-βl), mammastatin, neuregulin (NDF), mammary derived growth inhibitor (MDGI) and mammary-derived growth inhibitorrelated gene (MRG). Take transforming growth factor beta as an example, powerful inhibition of mammary gland growth and morphogenesis was observed. Mammastatin, a polypeptide purified from conditioned media of normal mammary epithelial cells, blocked DNA synthesis in cultured normal and transformed mammary epithelial cells. More recently identified MDGI and MRG exhibited inhibitory effect on proliferation of breast cancer cells and suppression of breast tumor growth in nude mouse model. These findings indicated that enhancement of the expression of growth inhibitors in breast cancer would provide potential strategies for tumor growth inhibition.In the present study, we found a novel gene (GenBank accession No. AY037158) by large-scale random sequencing. The 1766bp full-length novel cDNA was isolated from the cDNA library of human bone marrow stromal cells (BMSC). It is composed of a single 1434-bp open reading frame (ORF) encoding a 477-residue protein with a calculated molecular mass of 51.99 kDa and an isoelectric point of 6.63, a 5'untranslating region (UTR) of 146 bp, and a 3' UTR of 186 bp. The presence of upstream in-frame stop codon in the 5' UTR indicated it was a full-length cDNA clone. The putative protein lacks an N-terminal signal peptide predicted by SOSUI (signal) program or transmembrane regions by the Tmpred program, which indicated that it might be a non-secretory, soluble protein. At amino acid level, the C-ierminal residues of the protein were identical to human OKL38 (pregnancy-induced growth inhibitor), a novel 317-residue protein that may play a vital role in the growth regulation and differentiation of breast epithelial cells, but was 160-residue longer. The chromosome mapping of both protein revealed that they located to the same place of chromosome 16q23.3. According to Ong CK et al, the protein identified by us may be a longer variant of the previously cloned OKL38. Blast Search in protein database revealed significant homologies with rat and mouse pregnancy-induced growth inhibitor (of overall protein sequence 82 % and 81 % identity, 90 % and 89 % similarity, respectively). Based on its sequence identity and similarity with the pregnancy-induced growth inhibitor, and its capacity of inhibiting tumor growth and proliferation (shown below), the protein was designated as BDGI (bone marrow stromal cells-derived growth inhibitor).The mRN A expression pattern of human BDGI was analyzed by Northern blot and RT-PCR. Northern blot analysis detected a major band of approximately 2.0Kb. Relatively high level of mRNA expression was observed in testis, liver and skeletal muscle. Relatively low level of mRNA expression was found hi spleen, heart, kidney and pancreas. No expression of BDGI was detected in thymus, prostate, ovary, small intestine, colon, PBL, brain, placenta and lung tissu...
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