Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Arch Med Res. 2010 May;41(4):297-301. doi: 10.1016/j.arcmed.2010.05.009.
Epidemiological and institutional studies have demonstrated an association between systemic sclerosis (SSc) and breast cancer. For example, breast cancer is one of the most common cancers seen in SSc patients, whereas a higher rate of cutaneous scleroderma appeared in a group in which SSc followed breast cancer diagnosis. Additionally, sex hormones and genetic factors within the estrogen receptor (ER) influence the development of SSc and breast cancer. An older age at diagnosis of SSc, lack of antinuclear antibody positivity and the presence of pulmonary fibrosis are shown to be associated with the development of breast cancer in SSc patients. On the other hand, increased mammographic densities that may be caused by SSc are an important risk factor for breast cancer development. Despite the evidence that SSc and breast cancer are epidemiologically linked, the cause of this correlation is unclear. Caveolin-1 (Cav-1) is a negative regulator that inhibits the basal activity of several pro-proliferative and oncogenic proteins. Cav-1 regulated TGF-beta/Smad signaling appears to participate in the pathogenesis of breast cancer and tissue fibrosis in SSc. Thus, it is proposed that Cav-1 regulated TGF-beta/Smad signaling via Cav-1 scaffolding domain (CSD) may play a key role in the link between SSc and breast cancer by suppressing TGF-beta-mediated phosphorylation of Smad. Future studies of Cav-1 regulated TGF-beta/Smad signaling may lead to novel insights into the link between SSc and breast cancer and may also lead to new strategies for the management of these two fatal diseases.
流行病学和机构研究表明，系统性硬化症（SSc）和乳腺癌之间存在关联。例如，乳腺癌是 SSc 患者中最常见的癌症之一，而在一组 SSc 紧随乳腺癌诊断之后，皮肤硬皮病的发生率更高。此外，雌激素受体（ER）内的性激素和遗传因素影响 SSc 和乳腺癌的发展。研究表明，SSc 的诊断年龄较大、抗核抗体阳性率低和肺纤维化的存在与 SSc 患者乳腺癌的发展有关。另一方面，可能由 SSc 引起的乳腺密度增加是乳腺癌发展的重要危险因素。尽管有证据表明 SSc 和乳腺癌在流行病学上相关，但这种相关性的原因尚不清楚。窖蛋白-1（Cav-1）是一种负调节因子，可抑制几种促增殖和致癌蛋白的基础活性。Cav-1 调节的 TGF-β/Smad 信号似乎参与了乳腺癌和 SSc 中的组织纤维化的发病机制。因此，有人提出，Cav-1 通过 Cav-1 支架结构域（CSD）调节 TGF-β/Smad 信号可能通过抑制 TGF-β 介导的 Smad 磷酸化在 SSc 和乳腺癌之间发挥关键作用。对 Cav-1 调节的 TGF-β/Smad 信号的进一步研究可能会深入了解 SSc 和乳腺癌之间的联系，并为这两种致命疾病的治疗提供新的策略。
