The full-length sequence of the human metalloreductase STEAP1 (1-339aa) is tagged with 10xHis-SUMO-tag at the N-terminus, forming a target gene that is amplified through PCR. These amplified genes are inserted into expression vectors to generate recombinant plasmids, which are cultured in an in vitro E.coli expression system. The supernatant from the culture medium is purified by affinity chromatography, obtaining the recombinant human STEAP1 protein with a purity exceeding 90% as determined by SDS-PAGE.
The human STEAP1 protein is a membrane-bound protein characterized by its six transmembrane domains, which suggest a potential role as a transporter or ion channel within epithelial tissues. STEAP1 is predominantly expressed in prostate cancer and other malignancies, including bladder, colorectal, and ovarian cancers, where it is often associated with poor prognosis and tumor progression [1][2][3][4].
Functionally, STEAP1 is believed to participate in intercellular communication and the transport of small molecules between adjacent cells, particularly at cell-cell junctions [5][6]. This capability may contribute to its role in promoting cell proliferation and survival, as it has been shown to elevate reactive oxygen species levels, which can influence various cellular processes [1][7]. Additionally, STEAP1 has been implicated in mitochondrial electron transfer and metal ion metabolism, suggesting a multifaceted role in cellular homeostasis and cancer biology [1][7][8].
The expression of STEAP1 is often upregulated in cancerous tissues compared to adjacent normal tissues, correlating with aggressive tumor characteristics and higher Gleason scores in prostate cancer [4][3][9]. Its overexpression has been linked to reduced overall survival rates in various cancers, making it a promising target for therapeutic interventions [2][6][9]. Moreover, STEAP1's restricted expression in normal tissues relative to its high expression in tumors makes it an attractive candidate for targeted therapies, such as antibody-drug conjugates [6][10][11].
References:
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[6] C. Boswell, E. Mundo, C. Zhang, D. Bumbaca, N. Valle, K. Kozaket al., Impact of drug conjugation on pharmacokinetics and tissue distribution of anti-steap1 antibody–drug conjugates in rats, Bioconjugate Chemistry, vol. 22, no. 10, p. 1994-2004, 2011. https://doi.org/10.1021/bc200212a
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[11] J. Carrasquillo, B. Fine, N. Pandit‐Taskar, S. Larson, S. Fleming, J. Foxet al., Imaging patients with metastatic castration-resistant prostate cancer using89zr-dfo-mstp2109a anti-steap1 antibody, Journal of Nuclear Medicine, vol. 60, no. 11, p. 1517-1523, 2019. https://doi.org/10.2967/jnumed.118.222844
