The Septin-Binding Protein Anillin Is Overexpressed in Diverse Human Tumors

Abstract

Anillin is an actin-binding protein that can bind septins and is a component of the cytokinetic ring.We assessed the anillin expression in 7,579 human tissue samples and cell lines by DNA microarray analysis. Anillin is expressed ubiquitously but with variable levels of expression, being highest in the central nervous system. The median level of anillin mRNA expression was higher in tumors than normal tissues (median fold increase 2.58; 95% confidence intervals, 2.19-5.68, P < 0.0001) except in the central nervous system where anillin mRNA levels were lower in tumors.We developed a sensitive reverse transcription-PCR strategy to show that anillin mRNA is expressed in cell lines and in cDNA panels derived from fetal and adult tissues, thus validating the microarray data. We compared anillin with Ki67 mRNA expression and found a significant linear relationship between anillin and Ki67 mRNA expression (Spearmann r f 0.6, P < 0.0001). Anillin mRNA expression was analyzed during tumor progression in breast, ovarian, kidney, colorectal, hepatic, lung, endometrial, and pancreatic tumors and in all tissues there was progressive increase in anillin mRNA expression from normal to benign to malignant to metastatic disease. Finally, we used anti-anillin sera and found nuclear anillin immunoreactivity to be widespread in normal tissues, often not correlating with proliferative compartments. These data provide insight into the existence of nonproliferation-associated activities of anillin and roles in interphase nuclei. Thus, anillin is overexpressed in diverse common human tumors, but not simply as a consequence of being a proliferation marker. Anillin may have potential as a novel biomarker.

Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model

“…The same phenomenon is observed for ANLN (Fig. 3F), which has been shown to be overexpressed in many tumor types (22). It is tempting to speculate that this group of up-regulated genes reflects one single hallmark of cancer-increased proliferative signaling.…”

Anillin expression is a marker of favourable prognosis in patients with renal cell carcinoma

“…We further proved the cytoplasmic expression of anillin in a human renal cell carcinoma cell line using cytosolic and nuclear fractions in Western blot analysis. Cytoplasmic immunostaining of anillin has been observed previously (11), but it was obviously considered to comprise unspecific binding in immunohistochemistry. However, cytoplasmic expression of anillin has been reported during interphase (9), which supports our findings.…”

“…The median level of anillin mRNA was found to be higher in tumours than in normal tissues, with the exception of the CNS where anillin mRNA levels were higher in normal tissues than in tumours (11). Anillin mRNA expression has been studied during tumour progression in breast, ovarian, kidney, colorectal, hepatic, lung, endometrial and pancreatic tumours (11,22).…”

“…It was originally identified as an actin-binding protein (8) but it also binds non-muscle myosin II (7) and at least some septins (9,10). Anillin expression has been detected in several carcinomas (11).…”

“…The Ki-67 antigen is a well-characterized proliferation marker and its expression is linked with growth fraction of tumour cells (13). Of note, a significant linear relationship was detected between anillin and Ki-67 mRNA expressions in colorectal, lung, breast and lymphoid tissues (11).…”