Grant Blaine, Sundaram Buitrago Paola Alejandra, Mercado Beatriz C, Yajima Mamiko
Department of Molecular Biology Cell Biology Biochemistry, Brown University, Providence, Rhode Island, USA.
Dev Dyn. 2024 Mar;253(3):333-350. doi: 10.1002/dvdy.656. Epub 2023 Sep 12.
Some marine invertebrate organisms are considered not to develop tumors due to unknown mechanisms. To gain an initial insight into how tumor-related genes may be expressed and function during marine invertebrate development, we here leverage sea urchin embryos as a model system and characterize the expressions of Myc and p53/p63/p73 which are reported to function synergistically in mammalian models as an oncogene and tumor suppressor, respectively.
During sea urchin embryogenesis, a combo gene of p53/p63/p73 is found to be maternally loaded and decrease after fertilization both in transcript and protein, while Myc transcript and protein are zygotically expressed. p53/p63/p73 and Myc proteins are observed in the cytoplasm and nucleus of every blastomere, respectively, throughout embryogenesis. Both p53/p63/p73 and Myc overexpression results in compromised development with increased DNA damage after the blastula stage. p53/p63/p73 increases the expression of parp1, a DNA repair/cell death marker gene, and suppresses endomesoderm gene expressions. In contrast, Myc does not alter the expression of specification genes or oncogenes yet induces disorganized morphology.
p53/p63/p73 appears to be important for controlling cell differentiation, while Myc induces disorganized morphology yet not through conventional oncogene regulations or apoptotic pathways during embryogenesis of the sea urchin.
一些海洋无脊椎动物被认为由于未知机制而不会发生肿瘤。为了初步了解肿瘤相关基因在海洋无脊椎动物发育过程中可能如何表达和发挥功能，我们在此利用海胆胚胎作为模型系统，对Myc以及p53/p63/p73的表达进行了表征，据报道，在哺乳动物模型中，它们分别作为癌基因和肿瘤抑制基因协同发挥作用。
在海胆胚胎发生过程中，发现p53/p63/p73的一个组合基因在母本中就已存在，受精后其转录本和蛋白质水平均下降，而Myc转录本和蛋白质是合子表达的。在整个胚胎发生过程中，分别在每个卵裂球的细胞质和细胞核中观察到p53/p63/p73和Myc蛋白。p53/p63/p73和Myc的过表达均导致发育受损，囊胚期后DNA损伤增加。p53/p63/p73增加了DNA修复/细胞死亡标记基因parp1的表达，并抑制了内胚层基因的表达。相比之下，Myc不会改变特异性基因或癌基因的表达，但会诱导形态紊乱。
p53/p63/p73似乎对控制细胞分化很重要，而Myc在海胆胚胎发生过程中诱导形态紊乱，但不是通过传统的癌基因调控或凋亡途径。
