Transforming Acidic Coiled-Coil-Containing Protein 2 (TACC2) in Human Breast Cancer, Expression Pattern and Clinical/Prognostic Relevance.

Abstract

BACKGROUND: TACC2 is a member of the transforming acidic coiled-coil-containing protein family and is associated with the centrosome-spindle apparatus during cell cycling. In vivo, the TACC2 gene is expressed in various splice forms predominantly in postmitotic tissues, including heart, muscle, kidney, and brain. Recent work has shown that members of this family, including TACC2, may be involved in the progression of certain solid tumours. The aim of the current study was to identify the role of TACC2 in breast cancer and to establish if a prognostic relevance exists.MATERIALS AND METHODS: Fresh frozen primary human breast cancer tissues (n = 120) and non-neoplastic mammary tissues (n = 32) were used. The distribution and location of TACC2 was assessed using immunohistochemical staining (IHC) and imaging analysis tools. The transcript levels of TACC2 were determined using quantitative real time-PCR. The results were analyzed against the clinical, pathological and follow-up (10 years) data. Statistical analysis was by Mann-Whitney U test and Kaplan-Meier method. Shown are median transcript level.RESULTS: TACC2 protein staining was seen in both normal epithelial cells and cancer cells in mammary tissues. Increased staining of TACC2 was seen in most of the breast tumours examined when compared with normal breast tissues. Quantitative analysis of the TACC2 transcript also revealed a higher level expression in tumours compared with normal tissues (p=0.027, tumours vs normal). TACC2 expression was significantly increased in higher grade tumours compared to those in lower grade tumours (grade-3 vs grade-1, p=0.046). Using the Nottingham Prognostic Index (NPI), TACC2 transcript was significantly higher in tumours from patients with a moderate prognosis than from those with a good prognosis (p = 0.019). The expression in samples from patients with poor clinical outcome (with metastasis, recurrence and breast cancer related death) was significantly higher than that from patients who remained disease free (median (IQR) 33.8 (3.0-110.2) copies vs 6 (1.6-28.9) copies, p=0.038). This was reflected by the shorter disease-free survival for patients with high TACC2 (107 (91-122.8, 95% CI) months compared with 137 (125-150.6) months for patients with low TACC2 transcripts (p=0.019).CONCLUSION: This study shows that increased expression of TACC2 correlates with poor prognosis in patients with breast cancer. This suggests that TACC2 mediates an oncogenic effect on breast cancer cells. The findings also suggest that TACC2 may be a potential therapeutic target. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3159.

miR-25 promotes glioma cell proliferation by targeting CDKN1C

“…3A). These transcripts have been previously shown to be involved in the development of several cancers [20][21][22][23][24]. To evaluate whether miR-25 downregulates the expression of these genes, we first cloned the 3 0 UTR encoding sequences of these genes containing putative miR-25 binding sites into hRluc/TK luciferase reporter vector and individually cotransfected these vectors with miR-25 expressing plasmids into T98G and U373 cells.…”

The clinical significance of transforming acidic coiled-coil protein 3 expression in non-small cell lung cancer

“…In addition, the deregulation of human TACCs (TACC1-3) may be involved in the development and progression of some human malignancies (3,10,13,15,25,30,31).…”

“…The TACC family contains TACC1, TACC2 and TACC3 in mammals (2)(3)(4)10). Although increasing evidence indicates that abnormalities in human TACCs (TACC1-3) may correlate with the development of some human malignancies, the functions of these three proteins in mammals are largely unknown (11)(12)(13).…”

“…The human TACC1-3 genes are located on chromosome 8p11, 10q26 and 4p16.3, respectively (2,4,(11)(12)(13)(14)(15)(16)(17). TACC3 is mainly expressed in the developing embryo and in adult testis, thymus, peripheral blood leukocytes, spleen and intestinal tissues (4,17).…”

Harnessing Omics Big Data in Nine Vertebrate Species by Genome-Wide Prioritization of Sequence Variants with the Highest Predicted Deleterious Effect on Protein Function

“…postmitotic tissues, including heart, muscle, kidney, and brain (Cheng et al, 2010). Due to its important role in cell division, it is not surprising that it might play a role in some forms of cancer (Ha et al, 2013;Lauffart et al, 2003), particularly in prostate (Takayama et al, 2012) and breast cancer (Onodera et al, 2016).…”