The 57 kDa antigen recognized by the Ki-1 antibody, is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7% identity and 67.4% similarity with serpin mRNA binding protein 1, which is also named CGI-55, or plasminogen activator inhibitor type-1-RNA binding protein-1, indicating that they might be paralog proteins, possibly with similar or redundant functions in human cells. Through the identification of their protein interactomes, both regulatory proteins have been functionally implicated in transcriptional regulation, mRNA metabolism, specifically RNA splicing, the regulation of mRNA stability, especially, in the context of the progesterone hormone response, and the DNA damage response. Both proteins also show a complex pattern of post-translational modifications, involving Ser/Thr phosphorylation, mainly through protein kinase C, arginine methylation and SUMOylation, suggesting that their functions and locations are highly regulated. Furthermore, they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies, upon stress, and nuclear splicing speckles. Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis. This review highlights important aspects of the structure, interactome, post-translational modifications, sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.

• Cancer
• Cell signaling
• Regulatory protein
• Protein interactions
• Post-translational modifications

Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level.

Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression.

SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer.

The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the plasminogen activator protease cascade warrants further investigation.

• Bone Neoplasms/genetics
• Bone Neoplasms/pathology
• Connective Tissue Growth Factor
• Cysteine-Rich Protein 61
• Extracellular Matrix/metabolism
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immediate-Early Proteins/biosynthesis
• Intercellular Signaling Peptides and Proteins/biosynthesis
• Matrix Metalloproteinases/biosynthesis
• Mitochondria/physiology
• Neoplasm Invasiveness/genetics
• Osteosarcoma/genetics
• Osteosarcoma/pathology
• Oxidative Phosphorylation
• Phenotype
• Plasminogen Inactivators/biosynthesis
• Protease Inhibitors
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription, Genetic
• Tumor Cells, Cultured
• Urokinase-Type Plasminogen Activator/biosynthesis

• R01 CA085700-05A1 NCI NIH HHS
• R01 EY010804 NEI NIH HHS
• R01 CA085700-06 NCI NIH HHS
• CA-85700 NCI NIH HHS
• R01 EY010804-10 NEI NIH HHS
• EY-10804 NEI NIH HHS
• R01 EY010804-09 NEI NIH HHS
• R01 CA085700 NCI NIH HHS