Branch Kaitlin M, Garcia Erica C, Chen Yin Maggie, McGregor Matthew, Min Mikayla, Prosser Rachel, Whitney Natalia, Spencer Juliet V
Department of Biology, University of San Francisco, San Francisco, CA 94117, USA.
Department of Biology, Texas Woman's University, Denton, TX 76204, USA.
Pathogens. 2021 May 23;10(6):641. doi: 10.3390/pathogens10060641.
Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.
乳腺癌是全球女性癌症死亡的主要原因。乳腺癌有许多已知的风险因素，但传染病的作用仍不明确。人巨细胞病毒（HCMV）是一种广泛传播的疱疹病毒，通常很少引发疾病。由于在乳腺肿瘤活检样本中检测到了HCMV，且其常通过人乳传播，我们研究了HCMV在乳腺肿瘤细胞中的复制情况。用绿色荧光蛋白（GFP）标记的源自细菌人工染色体的HCMV临床菌株TB40/E感染了四种对雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）这三种关键诊断标志物具有不同表达谱的人乳腺癌细胞系。荧光显微镜检查证实所有四种乳腺癌细胞系都支持病毒进入。从感染细胞中分离RNA，并通过聚合酶链反应（PCR）确认即刻早期（UL123）、早期（UL54）和晚期（UL111A）基因的表达。通过免疫印迹检测病毒蛋白，并且乳腺肿瘤细胞感染期间产生了病毒后代，培养上清液随后感染成纤维细胞就证明了这一点。这些结果表明乳腺肿瘤细胞支持HCMV的有效感染，这可能表明HCMV复制可能在乳腺癌进展中起作用。
