未经证实:越来越多的文献表明,阿片样蛋白基因家族成员(PROL1,SMR3A和SMR3B)的受调节表达与癌症有关。最近,PROL1的过度表达与前列腺癌有关,有证据表明在克服随着肿瘤生长而发展的缺氧屏障中起作用。本研究的主要目的是支持和扩大PROL1在前列腺癌的发展和进展中的作用的证据。
未经授权:我们设计了阿片样蛋白基因的敲除,PROL1,在LNCaP中,对雄激素敏感,人类前列腺癌,细胞系。使用异种移植试验,我们比较了注射的LNCaPPROL1敲除细胞系与亲本LNCaP和LNCaPPROL1过表达细胞系在去势和完整雄性小鼠中发展肿瘤的能力。我们使用RNAseq比较亲本和LNCaPPROL1敲除细胞系之间的整体基因表达。使用伤口闭合和3D球状体侵袭测定来比较亲本LNCaP细胞和过表达PROL1的LNCaP细胞之间的细胞运动和迁移。
UNASSIGNED:本研究表明,当注射到去势和完整的雄性小鼠中时,具有PROL1组合敲除的LNCaP细胞系无法发展成肿瘤。使用RNAseq比较亲本和LNCaPPROL1敲除细胞系之间的整体基因表达,我们证实了PROL1在调节与血管生成和肿瘤血液供应相关的分子途径中的作用,并确定了在与细胞运动和迁移相关的途径中的潜在作用。通过使用伤口闭合和3D球体侵入测定,我们证实,与亲本细胞相比,在LNCaP细胞中PROL1的过表达导致更大的细胞运动和迁移,提示PROL1过表达导致更具侵袭性的表型。
未经评估:总的来说,我们的研究增加了越来越多的证据,表明编码opiorphin的基因在癌症的发展和进展中起作用。PROL1对于注射LNCaP细胞的小鼠肿瘤的建立和生长是必不可少的,我们提供的证据表明,PROL1可能在向更具侵入性的进展中发挥作用,转移性和去势抵抗性前列腺癌(PrCa)。
UNASSIGNED: A growing body of literature suggests modulated expression of members of the opiorphin family of genes (PROL1, SMR3A and SMR3B) is associated with cancer. Recently, overexpression of PROL1 was shown to be associated with prostate cancer, with evidence of a role in overcoming the hypoxic barrier that develops as tumors grow. The primary goal of the present studies was to support and expand evidence for a role of PROL1 in the development and progression of prostate cancer.
UNASSIGNED: We engineered knock-out of the opiorphin gene, PROL1, in LNCaP, an androgen-sensitive, human prostate cancer derived, cell-line. Using xenograft assays, we compared the ability of injected LNCaP PROL1 knock-out cell-lines to develop tumors in both castrated and intact male mice with the parental LNCaP and LNCaP PROL1 overexpressing cell-lines. We used RNAseq to compare global gene expression between the parental and LNCaP PROL1 knock-out cell-lines. Wound closure and 3D spheroid invasion assays were used to compare cell motility and migration between parental LNCaP cells and LNCaP cells overexpressing of PROL1.
UNASSIGNED: The present studies demonstrate that LNCaP cell-lines with consisitutive knock-out of PROL1 fail to develop tumors when injected into both castrated and intact male mice. Using RNAseq to compare global gene expression between the parental and LNCaP PROL1 knock-out cell-lines, we confirmed a role for PROL1 in regulating molecular pathways associated with angiogenesis and tumor blood supply, and also identified a potential role in pathways related to cell motility and migration. Through the use of wound closure and 3D spheroid invasion assays, we confirmed that overexpression of PROL1 in LNCaP cells leads to greater cell motility and migration compared to parental cells, suggesting that PROL1 overexpression results in a more invasive phenotype.
UNASSIGNED: Overall, our studies add to the growing body of evidence that opiorphin-encoding genes play a role in cancer development and progression. PROL1 is essential for establishment and growth of tumors in mice injected with LNCaP cells, and we provide evidence that PROL1 has a possible role in progression towards a more invasive, metastatic and castration resistant prostate cancer (PrCa).