HPV Status and Its Correlation with BCL2, p21, p53, Rb, and Survivin Expression in Breast Cancer in a Chinese Population

Abstract

Despite recent evidence, the role of human papillomavirus (HPV) in breast carcinogenesis is controversial. The correlations of HPV infection with the clinicopathological features of breast cancer and the expression of cell cycle/apoptosis-associated proteins have not been well elucidated. In this study, we sought to determine the prevalence of high-risk HPVs (HR-HPVs) infection and BCL2, p21, p53, Rb, and survivin expression in breast cancer patients and to investigate the relationship of HPV with these cancer-related proteins, in an attempt to clarify the potential mechanism of HPV in breast cancer pathogenesis. HPV presence in 81 fresh breast cancer tissues was determined by hybrid capture 2 (HC2) assay, and expression of BCL2, p21, p53, Rb, and survivin was detected by immunohistochemistry. Here we showed that fourteen (17.3%) patients were HR-HPV positive. HPV infection demonstrated no significant correlation with the clinicopathological characteristics of breast cancer. HPV-positive tumors showed significantly higher BCL2 and lower p53 expression than HPV-negative tumors. Expression of p21, Rb, and survivin was not associated with HPV status. Our results suggest a possible role of HR-HPV in breast cancer carcinogenesis, in which BCL2 and p53 may be involved.

Epstein–Barr Virus and Human Papillomaviruses Interactions and Their Roles in the Initiation of Epithelial–Mesenchymal Transition and Cancer Progression

“…In this regard, E6/E7 onco-proteins of HPVs have been identified in breast cancer ( 109 ); though, there is a low level of transcription of these onco-proteins ( 110 ). Meanwhile, it has been reported that the presence of HPVs in breast cancer is associated with more aggressive phenotype ( 9 , 82 , 103 , 111 ).…”

High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis

“…Specific techniques have been used to detect the low level of HPV in these samples. These techniques include in situ PCR [ 18 , 19 ], histology [ 14 ], bead-based Luminex technology [ 20 ], hybrid capture 2 (HC2) assay [ 21 ], and HPV capture paired with massive paralleled sequencing [ 22 ]. The low levels of HPV detected in these patients does not discount HPV from having a causative role.…”

Saikosaponin D inhibits proliferation of human osteosarcoma cells via the p53 signaling pathway

“…Bcl-2 family proteins serve central roles in mitochondria-mediated apoptosis and are divided into three groups: BH3-only proteins, BAX/bcl-2 homologous antagonist/killer (BAK) proteins and pro-survival proteins (34). Activated BAX/BAK forms homo-oligomers that permeabilize mitochondria and allow the release of pro-apoptotic factors, such as cytochrome c, which promote the activation of caspases (35,36). In the present study, SSd significantly increased transcription of p53 and its downstream targets, including p21, p27 and Bax, and decreased cyclinD1 expression.…”

“…In the present study, SSd significantly increased transcription of p53 and its downstream targets, including p21, p27 and Bax, and decreased cyclinD1 expression. CyclinD1 has been demonstrated to activate the G1-S transition of the cell cycle (35,36). Gumz et al (37) reported that cyclinD1 was up-regulated in clear cell RCC and that an antagonist of the Wnt signaling pathway, sFRP1, inhibited cyclinD1 expression.…”