The role of the multi‐drug resistance 1, p53, b cell lymphoma 2, and bcl 2‐associated X genes in the biologic behavior and chemotherapeutic resistance of canine transmissible venereal tumors

Abstract

BackgroundCanine transmissible venereal tumors (CTVTs) generally have different cytomorphologic subtypes and phases of progression. Some tumors have variable biologic behavior including a progressive increase in tumor aggressiveness and variable responses to chemotherapy. This behavior is partially due to high p‐glycoprotein expression by tumor cells, which leads to the expulsion of chemotherapeutic drugs. Other possible causes include changes in pro‐ and anti‐apoptotic genes from the BCL‐2 family and DNA repair systems, which are associated with the p53 gene family.ObjectivesWe aimed to determine the relative expression of the multi‐drug resistance 1 (MDR1), p53, b‐cell lymphoma 2 (BCL2), and bcl 2‐associated X (BAX) genes in CTVT before and after therapy and establish a relationship with treatment responses, cytomorphologic patterns, and tumor progression identified with histopathology.MethodsRT‐qPCR was performed on 21 CTVT tumor samples before and after initiating chemotherapy to determine specific gene expression. Normal canine testicular tissue was used as a negative control for all experiments.ResultsMDR1 expression was decreased before and after initiating vincristine therapy in CTVT tumor tissues compared with normal canine testicular tissue; p53 and BAX were overexpressed at both time points compared with normal tissue, and no statistical differences were seen between the different morphologic types. However, BAX expression was decreased in the group with quick therapeutic responses but was still overexpressed compared with normal testicular tissue. In the group with the slowest chemotherapeutic responses, BCL2 was overexpressed.ConclusionThe findings of this study showed a relative increase in MDR1 gene expression in response to chemotherapy and higher expression in plasmacytoid CTVTs compared with the other cytomorphologic patterns. BCL2 overexpression was related to a favorable prognosis, and p53, BAX, and BCL2 were expressed independent of the cytomorphologic CTVT type. All of the genes were expressed independent of tumor progression, as noted on histopathology.

Expression of PCNA, MMP-9, p53, Bax and Bcl-2 in canine transmissible venereal tumors

“…The protein X associated with BCL2 (Bax) is a proapoptotic protein that triggers mitochondrial membrane permeability in response to apoptotic stimuli. In contrast, Bcl-2 is an anti-apoptotic protein that protects cell death (Alzate et al, 2019). In the antiapoptotic effect of Bcl-2, it is important to stabilize the mitochondrial membrane and prevent the release of cytochrome-c (Lokesh et al;.…”

“…Once the tumor has settled, it can proliferate and spread to other locations in the body and eventually become metastatic. (Alzate et. al., 2019).…”

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

“…To date, in CTVT, there have been no reports on BCL-xL expression; however, BCL-2 expression has been identified, as well as mutations in TP53 (CHOI & KIM, 2002;VÁZQUEZ-MOTA et al, 2008;ALZATE et al, 2009;STOCKMANN et al, 2011;FLÓREZ et al, 2017). However; although, there is evidence of mutations of the TP53 gene in CTVT, the ability of this mutation to cause functional changes in the protein, as well as in the tumor evolution remains unknown (VÁZQUEZ-MOTA et al, 2008).…”

Anticancer effects and the mechanism underlying 2‑methoxyestradiol in human osteosarcoma <em>in&nbsp;vitro</em> and <em>in&nbsp;vivo</em>

“…Tumor growth is inseparable from sustained and extensive angiogenesis, and inhibition of neovascularization of tumors may be an effective method for treating tumors (27). As the expression of VEGF is closely associated with angiogenesis and tumor cell proliferation, inhibiting and blocking the biological activity of VEGF secreted by tumor cells is important for suppressing tumor growth and metastasis (28).…”

“…Bcl-2 activation and abnormal expression is associated with the occurrence and development of tumors ( 27 ). It also plays an important role in the formation of multidrug resistance in tumors ( 28 ). Numerous studies have confirmed that the Bcl-2 gene is closely associated with the occurrence of a variety of malignant tumors ( 29 – 31 ).…”