Alternative titles; symbols
HGNC Approved Gene Symbol: SCGB2A2
Cytogenetic location: 11q12.3 Genomic coordinates (GRCh38) : 11:62,270,158-62,273,160 (from NCBI)
Using a modified differential display PCR technique, Watson and Fleming (1994) isolated sequence fragments that were abundantly expressed in a breast tumor relative to normal breast tissue. Using this fragment, RT-PCR, and RACE, Watson and Fleming (1996) isolated a novel full-length cDNA clone, which they designated mammaglobin-1 (MGB1). MGB1 encodes a deduced 93-amino acid protein with a 19-amino acid hydrophobic peptide signal sequence and a predicted molecular mass of 10.5-kD. The protein shares 42% sequence identity with the rat prostatein protein (rPSC3). It also shares high homology with rabbit and human uteroglobin (UGB; 192020) genes, including the conservation of cysteines known to play a role in disulfide bond formation between uteroglobin subunits and a conserved tyrosine required for progesterone binding to the uteroglobin dimer. Watson et al. (1998) reported that the arrangement and splice sites of the 3 exons of MGB1, UGB, and rPSC3 are well conserved, suggesting that these genes constitute a multigene family derived from a common ancestral sequence. The mammaglobin gene itself, however, is not well conserved phylogenetically.
Because other uteroglobin gene family members are regulated by steroid hormones, Watson et al. (1998) analyzed the MGB1 gene promoter for steroid-responsive elements. They identified 2 imperfect elements similar to estrogen- and androgen-response elements. Additionally, the promoter contains a polyoma enhancer-related (PEA3, or ETV4; 600711) motif. PEA3 is associated with activation of vimentin (193060) transcription in mammary epithelial cells and overexpression of ERBB2 (164870) in human breast tumors. Watson et al. (1998) also identified binding sites for the Sp family of transcription factors, an Ap-1 consensus site, and a binding site similar to the binding site of pregnancy-specific mammary factor in the MGB1 promoter. They did not observe any modulation of MGB1 transcription by estradiol, progesterone, dexamethasone, or androgens.
Using Northern blot analysis and RT-PCR, Watson and Fleming (1996) detected low level, breast-restricted expression of a 0.5-kb MGB1 transcript. They also detected MGB1 expression in several breast carcinoma cell lines but not in primary breast myoepithelial cells, primary breast stromal cells, an immortalized breast cell line, or an immortalized luminal ductal breast cell line. In the cell lines displaying the highest levels of expression, they also detected a 3-kb transcript, which they hypothesized was unprocessed nuclear mRNA. Watson and Fleming (1996) found that 8 of 35 primary breast carcinomas overexpressed MGB1 relative to normal breast tissue specimens, and Watson et al. (1998) found that 5 of 10 breast carcinoma cell lines and 13 of 21 metastatic breast tumors exhibited high levels of MGB1 mRNA. The overexpression did not appear to correlate with histology, tumor grade, tumor stage, or hormone receptor status. Watson and Fleming (1996) concluded that MGB1 expression is mammary-specific and may define a unique phenotype to a subset of breast carcinoma cell lines. Watson et al. (1998) presented preliminary data suggesting that expression of MGB1 is not associated with lactation, but instead with mammary gland proliferation and terminal differentiation.
The human MGB1 gene comprises 3 exons (Watson et al., 1998).
By fluorescence in situ hybridization and radiation hybrid analysis, Watson et al. (1998) mapped the MGB1 gene to 11q12.3-q13.1. They detected a second FISH signal on 15q23-q24, indicating a possible homologous gene sequence. Chromosome 11q13 is frequently amplified in breast carcinomas, but Watson et al. (1998) did not detect gene amplification or gross rearrangements in breast tumors or cell lines.
Watson, M. A., Darrow, C., Zimonjic, D. B., Popescu, N., Fleming, T. P. Structure and transcriptional regulation of the human mammaglobin gene, a breast cancer associated member of the uteroglobin gene family localized to chromosome 11q13. Oncogene 16: 817-824, 1998. [PubMed: 9488047] [Full Text: https://doi.org/10.1038/sj.onc.1201597]
Watson, M. A., Fleming, T. P. Mammaglobin, a mammary-specific member of the uteroglobin gene family, is overexpressed in human breast cancer. Cancer Res. 56: 860-865, 1996. [PubMed: 8631025]
Watson, M. A., Fleming, T. P. Isolation of differentially expressed sequence tags from human breast cancer. Cancer Res. 54: 4598-4602, 1994. [PubMed: 8062249]