Do alterations in gene expressions influence tumorigenesis in the transmissible venereal tumor in dogs?

ABSTRACT: Canine transmissible venereal tumor (CTVT) is a transmissible neoplasm, which spreads naturally between dogs through the halogenic transfer of tumor cells, mainly during coitus. It is the oldest known tumoral lineage in nature and reports on gene mutations have been extended. Also, this tumor shares several genetic mutations with some cancers in humans, among them lung carcinomas, melanoma, prostate, breast, among other cancers. Thus, expression of tumor suppressor genes such as TP53, P21, and apoptosis-related genes such as BAX, BCL-2, and BCL-xL, both in vivo and in vitro (primary cell culture) were quantified. In the present study, the comparison of gene expression, the TP53 gene, in most cases, was shown to be high in the majority of tissues (65%) and primary cell culture (100%), while BCL-2, BCL-xL, and BAX presented variation among the animals analyzed. Moreover, in these situations, the results suggested that the apoptotic regulation of these genes did not occur for TP53. The P21 gene was shown to be mostly normal (70%); although, absence (6%) and underexpressions (24%) were also observed. Statistical analysis of the BCL-xL gene demonstrated significant differences between the tissues of the animals when compared to the cell cultures; however, to the other genes, no statistical difference was observed between the groups. Preliminarily, the results suggested the presence of alterations in the gene expressions of the TP53, P21, BAX, BCL-2 and BCL-xL leading to loss of function in these genes, which affect the tumorigenesis of CTVT.

摘要：犬传染性生殖器官肿瘤（Canine transmissible venereal tumor, CTVT）是一种传染性肿瘤，可通过肿瘤细胞的卤代转移（halogenic transfer）自然传播于犬只之间，主要发生于交配过程中。该肿瘤是自然界中已知的最古老的肿瘤细胞系，目前关于其基因突变的研究报道已日趋丰富。此外，该肿瘤与人类的多种癌症存在共有的基因突变，包括肺癌、黑色素瘤、前列腺癌、乳腺癌等其他恶性肿瘤。因此，本研究对体内（in vivo）、体外（in vitro，原代细胞培养（primary cell culture））环境下的抑癌基因（如TP53、P21）以及凋亡相关基因（如BAX、BCL-2、BCL-xL）的表达水平进行了定量检测。在本次基因表达比较分析中，TP53基因在多数受试肿瘤组织（65%）及原代细胞培养体系（100%）中均呈高表达状态；而BCL-2、BCL-xL与BAX的表达水平在受试动物个体间存在显著异质性。此外，上述结果提示，TP53并未参与上述基因的凋亡调控通路。P21基因的表达水平大多处于正常范围（70%），但仍有6%的样本呈完全不表达，24%的样本呈低表达状态。对BCL-xL基因的统计学分析显示，受试动物的肿瘤组织与细胞培养体系间的基因表达水平存在显著差异；但其余基因在两组样本间未检测到统计学差异。本研究初步结果表明，TP53、P21、BAX、BCL-2及BCL-xL的基因表达存在异常，导致上述基因功能丧失，进而影响CTVT的肿瘤发生进程。