Ford Caroline E, Faedo Margaret, Rawlinson William D
Virology Division, Department of Microbiology, South Eastern Sydney Area Laboratory Services, Prince of Wales Hospital, Randwick, Australia.
Clin Cancer Res. 2004 Nov 1;10(21):7284-9. doi: 10.1158/1078-0432.CCR-04-0767.
Identifiable risk factors for the development of breast cancer include age, diet, family history, and lifetime estrogen exposure. An infectious agent (mouse mammary tumor virus; MMTV) is known to cause murine breast tumors and may be involved in the pathogenesis of human disease. Multiple studies have detected MMTV-like sequences in 30 to 60% of breast cancer samples and up to 1.8% of samples from normal breast. Using in situ PCR of MMTV-like sequences of formalin-fixed, paraffin-embedded breast tissue, viral sequences have been located in cancerous epithelial cells in breast acini of male and female breast tumors, but not in adjacent nonmalignant cells. MMTV-like sequences were also located in the epithelial cells of male gynecomastia samples. Using reverse transcriptase in situ PCR, RNA transcripts from the env gene were also detected within cancerous epithelial cells of 78% of DNA-positive tumors, 80% of gynecomastia samples, and 0% of normal tissues screened. This suggests the virus may be replicating in these cells. The epidemiologic and histopathological data are consistent with the association of an MMTV-like virus with breast cancers in men and women. The association with gynecomastia, a benign, possibly premalignant condition suggests hormonal influences, rather than cancer per se, may be the dominant factor in determining viral presence and replication.
乳腺癌发生的可识别风险因素包括年龄、饮食、家族病史和终生雌激素暴露。已知一种传染因子(小鼠乳腺肿瘤病毒;MMTV)可引发鼠类乳腺肿瘤,并且可能参与人类疾病的发病机制。多项研究在30%至60%的乳腺癌样本以及高达1.8%的正常乳腺样本中检测到了MMTV样序列。通过对福尔马林固定、石蜡包埋的乳腺组织中MMTV样序列进行原位PCR,病毒序列已定位在男性和女性乳腺肿瘤腺泡的癌上皮细胞中,但未在相邻的非恶性细胞中发现。MMTV样序列也存在于男性乳腺增生症样本的上皮细胞中。使用逆转录原位PCR,在78%的DNA阳性肿瘤、80%的乳腺增生症样本以及所筛查的0%正常组织的癌上皮细胞中也检测到了来自env基因的RNA转录本。这表明该病毒可能在这些细胞中复制。流行病学和组织病理学数据与一种MMTV样病毒与男性和女性乳腺癌的关联相一致。与乳腺增生症(一种良性、可能为癌前病变的病症)的关联表明,激素影响而非癌症本身可能是决定病毒存在和复制的主导因素。