Dysregulated adenosine signaling pathway has been evidenced in the pathogenesis of breast cancer. However, the role of adenosine kinase (ADK) in tumorigenesis remains unclear while it crucially regulates the removal and availability of adenosine. ADK has two isoforms that localize to discrete subcellular spaces: i.e., nuclear, long-isoform (ADK-L) and cytosolic, short-isoform (ADK-S). We hypothesized that these two ADK isoforms would be differentially expressed in breast cancer and may contribute to divergent cellular actions in cancer. In this study, we examined the expression profiles of ADK isoforms in breast cancer tissues from 46 patient and followed up with an in vitro investigation by knocking down the expression of ADK-L or ADK-S using CRISPR gene editing to evaluate the role of ADK isoform in cancer progression and metastasis of cultured triple-negative breast cancer cell line MDA-MB-231. We demonstrated that (i) ADK-L expression level was significantly increased in breast cancer tissues versus paired normal tissues adjacent to tumor, whereas the ADK-S expression levels were not significantly different between cancerous and normal tissues; (ii) CRISPR/Cas9-mediated downregulation of ADK isoforms, led to suppressed cellular proliferation, division, and migration of cultured breast cancer cells; (iii) ADK-L knockdown significantly upregulated gene expression of matrix metalloproteinase (ADAM23, 9.93-fold; MMP9, 24.58-fold) and downregulated expression of cyclin D2 (CCND2,-30.76-fold), adhesive glycoprotein THBS1 (-8.28fold), and cystatin E/M (CST6,-16.32-fold). Our findings suggest a potential role of ADK-L in mitogenesis, tumorigenesis, and tumor-associated tissue remodeling and invasion; and the manipulation of ADK-L holds promise as a therapeutic strategy for aggressive breast cancer.
Research indicates that there is continuity in both maladaptive ( Chen & Kaplan, 2004 ) and positive parenting from one generation to the next. Within the topic of parenting, intergenerational transmission of specific parenting styles, specifically, the intergenerational transmission of authoritarian, permissive, and authoritative parenting styles has received limited attention in the research. In addition, few researchers have examined the impact of parenting styles applied to specific family members. As such, this study examined whether certain types of parenting styles may be passed down from parent to son. Through an online questionnaire, ( N = 28) men indicated, retrospectively, how they were parented and how they raise (or would raise) their children. The results of this study indicate a positive correlation between sons being parented in an authoritarian or permissive manner and subsequent engagement in the same parenting style.
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