The alternative protein isoform NK2B, encoded by the vnd/NK-2 proneural gene, directly activates transcription and is expressed following the start of cells differentiation

NK-2 is a homeodomain protein essential for the development of the central nervous system in the Drosophila embryo. Here, we show that the vnd/NK-2 gene encodes an additional protein isoform (NK-2B) that differs from the known one (NK-2A) in its N-terminal domain. While NK-2A is a transcription repressor, NK-2B directly activates transcription from promoters containing NK-2 binding sites, with its N-terminal domain possessing a strong transcription activation potency. The transcription of NK-2B starts at the onset of metamorphosis. Its expression is observed in precursors of differentiating photoreceptors and in photoreceptors of the adult eye. Both NK-2B and NK-2A are expressed in the lamina. However, the expression of NK-2A is mostly associated with the undifferentiated state of nervous cells

Suppression of OCT-1 in Metastatic Breast Cancer Cells Reduces Tumor Metastatic Potential, Hypoxia Resistance, and Drug Resistance

OCT-1/POU2F1 is a ubiquitously expressed transcription factor. Its expression starts at the earliest stage of embryonic development. OCT-1 controls genes involved in the regulation of differentiation, proliferation, cell metabolism, and aging. High levels of OCT-1 transcription factor in tumor cells correlate with tumor malignancy and resistance to antitumor therapy. Here, we report that suppression of OCT-1 in breast cancer cells reduces their metastatic potential and drug resistance. OCT-1 knockdown in the MDA-MB231 breast cancer cells leads to a fivefold decrease (p < 0.01) in cell migration rates in the Boyden chamber. A decrease in the transcription levels of human invasion signature (HIS) genes (ARHGDIB, CAPZA2, PHACTR2, CDC42, XRCC5, and CAV1) has been also demonstrated by real-time PCR, with high expression of these genes being a hallmark of actively metastasizing breast cancer cells. Transcriptional activity of ATF6 response elements is significantly reduced in the cell lines with decreased OCT-1 expression, which results in lower levels of adaptive EPR stress response. OCT-1 knockdown more than two times increases the MDA-MB231 cell death rate in hypoxia and significantly increases the doxorubicin or docetaxel-treated MDA-MB231 cell death rate. Our findings indicate that OCT-1 may be an important therapeutic target and its selective inhibition may have significant therapeutic effects and may improve prognosis in breast cancer patients