Calaf Gloria M, Abarca-Quinones Jorge
Institute for Advanced Research, Tarapacá University, Arica 1001236, Chile; Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA.
School of Medicine, Saint-Luc Hospital, IMAG Unit (IREC), University of Louvain, Brussels 1200, Belgium.
Oncol Lett. 2016 Jun;11(6):3637-3642. doi: 10.3892/ol.2016.4461. Epub 2016 Apr 19.
Breast cancer, the most common neoplasm in women of all ages, is the leading cause of cancer-related mortality in women worldwide. Markers to help to predict the risk of progression and ultimately provide non-surgical treatment options would be of great benefit. At present, there are no available molecular markers to predict the risk of carcinoma progression to invasive cancer; therefore, all women diagnosed with this type of malignancy must undergo surgery. Breast cancer is a heterogeneous complex disease, and different patients respond differently to different treatments. In breast cancer, analysis using immunohistochemical markers remains an essential component of routine pathological examinations, and plays an import role in the management of the disease by providing diagnostic and prognostic strategies. The aim of the present study was to identify a marker that can be used as a prognostic tool for breast cancer. For this purpose, we firstly used an established breast cancer model. MCF-10F, a spontaneously immortalized breast epithelial cell line was transformed by exposure to estrogen and radiation. MCF-10F cells were exposed to low doses of high linear energy transfer (LET) α particles (150 keV/μm) of radiation, and subsequently cultured in the presence of 17β-estradiol. Three cell lines were used: i) MCF-10F cells as a control; ii) Alpha5 cells, a malignant and tumorigenic cell line; and iii) Tumor2 cells derived from Alpha5 cells injected into nude mice. Secondly, we also used normal, benign and malignant breast specimens obtained from biopsies. The results revealed that the MCF-10F cells were negative for c-Ha-Ras protein expression; however, the Alpha5 and Tumor2 cell lines were positive for c-Ha-Ras protein expression. The malignant breast samples were also strongly positive for c-Ha-Ras expression. The findings of our study indicate that c-Ha-Ras protein expression may be used as a marker to predict the progression of breast cancer; this marker may also ultimately provide non-surgical treatment options for patients who are at a lower risk.
乳腺癌是各年龄段女性中最常见的肿瘤,是全球女性癌症相关死亡的主要原因。有助于预测疾病进展风险并最终提供非手术治疗方案的标志物将大有裨益。目前,尚无可用的分子标志物来预测癌进展为浸润性癌的风险;因此,所有被诊断患有此类恶性肿瘤的女性都必须接受手术。乳腺癌是一种异质性复杂疾病,不同患者对不同治疗的反应不同。在乳腺癌中,使用免疫组化标志物进行分析仍然是常规病理检查的重要组成部分,通过提供诊断和预后策略在疾病管理中发挥重要作用。本研究的目的是确定一种可作为乳腺癌预后工具的标志物。为此,我们首先使用了一个已建立的乳腺癌模型。MCF-10F是一种自发永生化的乳腺上皮细胞系,通过暴露于雌激素和辐射而发生转化。将MCF-10F细胞暴露于低剂量的高线性能量转移(LET)α粒子(150 keV/μm)辐射下,随后在17β-雌二醇存在的情况下进行培养。使用了三种细胞系:i)MCF-10F细胞作为对照;ii)Alpha5细胞,一种恶性且具有致瘤性的细胞系;iii)从注射到裸鼠体内的Alpha5细胞衍生而来的Tumor2细胞。其次,我们还使用了从活检中获得的正常、良性和恶性乳腺标本。结果显示,MCF-10F细胞的c-Ha-Ras蛋白表达为阴性;然而,Alpha5和Tumor2细胞系的c-Ha-Ras蛋白表达为阳性。恶性乳腺样本的c-Ha-Ras表达也呈强阳性。我们的研究结果表明,c-Ha-Ras蛋白表达可作为预测乳腺癌进展的标志物;该标志物最终也可能为低风险患者提供非手术治疗方案。