FAM83A is a potential biomarker for breast cancer initiation

Biomarker Research

Ram Podicheti¹  Sandra K. Althouse²  Harikrishna Nakshatri³  George E. Sandusky⁴  Rebekah J. Addison⁴  Constance J. Temm⁴  Bryce Selman⁴  Rana German⁵  Pam Rockey⁵  Anna Maria V. Storniolo⁶  Natascia Marino⁶ 

[1] Center for Genomics and Bioinformatics, Indiana University, 47405, Bloomington, IN, USA;Department of Biostatistics and Health Data Sciences, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Surgery, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Pathology and Laboratory Medicine, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Susan G. Komen Tissue Bank at the IU Simon Comprehensive Cancer Center, 46202, Indianapolis, IN, USA;Susan G. Komen Tissue Bank at the IU Simon Comprehensive Cancer Center, 46202, Indianapolis, IN, USA;Department of Medicine, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;

关键词: Normal breast;    FAM83A;    Breast cancer;    Cell transformation;   

DOI  :  10.1186/s40364-022-00353-9

来源: Springer

【 摘 要 】

BackgroundFamily with sequence similarity 83 member A (FAM83A) presents oncogenic properties in several cancers including breast cancer. Recently, we reported FAM83A overexpression in normal breast tissues from women at high risk of breast cancer. We now hypothesize that FAM83A is a key factor in breast cancer initiation.MethodsImmunohistochemical staining was used to evaluate FAM83A protein levels in both a normal breast tissue microarray (TMA, N = 411) and a breast tumor TMA (N = 349). EGFR staining and its correlation with FAM83A expression were also assessed. Lentivirus-mediated manipulation of FAM83A expression in primary and hTERT-immortalized breast epithelial cells was employed. Biological and molecular alterations upon FAM83A overexpression/downregulation and FAM83A’s interaction partners were investigated.ResultsTMA analysis revealed a 1.5-fold increase in FAM83A expression level in breast cancer cases as compared with normal breast tissues (p < 0.0001). FAM83A protein expression was directly correlated with EGFR level in both normal and breast cancer tissues. In in vitro assays, exogenous expression of FAM83A in either primary or immortalized breast epithelial cells promoted cell viability and proliferation. Additionally, Ingenuity Pathway Analysis (IPA) revealed that FAM83A overexpression in primary cells affected the expression of genes involved in cellular morphology and metabolism. Mass spectrometry analysis identified DDX3X and LAMB3 as potential FAM83A interaction partners in primary cells, while we detected FAM83A interaction with cytoskeleton reorganization factors, including LIMA1, MYH10, PLEC, MYL6 in the immortalized cells.ConclusionsThis study shows that FAM83A promotes metabolic activation in primary breast epithelial cells and cell proliferation in both primary and immortalized cells. These findings support its role in early breast oncogenesis.

【 授权许可】

CC BY