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Background/Aim: Activin and its antagonist follistatin (FST) have been implicated in several solid tumours. This study investigated the role of FST in breast cancer. Materials and Methods: FST expression was examined using reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry in a cohort of breast cancer samples. Expression was correlated to pathological and prognostic parameters in our patient cohort. FST was overexpressed in MCF-7 cells and assays for growth and invasion were performed. Results: FST is expressed in breast tissue, in the cytoplasm of mammary epithelial cells. Expression was decreased in breast cancer tissue in comparison to normal mammary tissue. Over-expression of FST in vitro led to significantly increased growth rate and reduced invasion. Higher FST associates with lower-grade tumours and better survival. Conclusion: Our results suggest a role for FST as a suppressor of invasion and metastasis in breast cancer.

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

The downstream of tyrosine kinase 7 (DOK7) is an adaptor protein mediating signalling transduction between receptors and intracellular downstream molecules. Reduced expression of DOK7 has been observed in breast cancer. The present study aimed to investigate the role played by DOK7 in lung cancer. The expression of DOK7 at both mRNA and protein levels was evaluated in human lung cancer. A reduced expression of DOK7 transcripts was seen in lung cancers compared with normal lung tissues. Kaplan-Meier analyses showed that the reduced expression of DOK7 was associated with poorer overall survival and progression-free survival of patients with lung cancer. A further western blot analysis revealed a predominant expression of DOK7 isoform 1 (DOK7V1) in normal lung tissues, which was reduced in lung cancer. Forced overexpression of DOK7V1 in lung cancer cell lines, A549 and H3122 resulted in a decrease of in vitro cell proliferation and migration, while adhesion to extracellular matrix was enhanced following the expression. In conclusion, DOK7 was reduced in lung cancer and reduced DOK7 expression was associated with poorer survival. DOK7 isoform 1 plays an inhibitory role on the proliferation and migration of lung cancer cells in which Akt pathway may be involved.

Follistatin (FST), as a single-chain glycosylated\ud protein, has two major isoforms, FST288 and FST315. The\ud FST315 isoform is the predominant form whilst the FST288\ud variant accounts for less than 5% of the encoded mRNA.\ud FST is differentially expressed in human tissues and aberrant\ud expression has been observed in a variety of solid tumours,\ud including gonadal, gastric and lung cancer, hepatocellular\ud carcinoma, basal cell carcinoma and melanoma. Based on\ud the current evidence, FST is an antagonist of transforming\ud growth factor beta family members, such as activin and bone\ud morphogenetic proteins (BMPs). FST plays a role in\ud tumourigenesis, metastasis and angiogenesis of solid\ud tumours through its interaction with activin and BMPs, thus\ud resulting in pathophysiological function. In terms of\ud diagnosis, prognosis and therapy FST has shown strong\ud promise. Through a better understanding of its biological\ud functions, potential clinical applications may yet emerge.

Phospholipase C (PLC) regulates a number of\ud cellular behaviours including cell motility, cell transformation,\ud differentiation and cell growth. PLC plays a regulatory\ud role in cancer cells partly by acting as signalling intermediates\ud for cytokines such as EGF and interleukins. The current\ud study examined the expression of the PLC isozymes in human\ud breast cancer and corresponding clinical relevance. Transcript\ud levels of human PLC-α, -β1, -δ, -ε, and -γ1 in human breast\ud cancer tissues were quantitatively determined by real-time\ud PCR. Immunochemical staining was performed for PLC-δ.\ud The clinical relevance was analysed with clinic pathological\ud information. Mammary tissues widely expressed PLC-α, -β1,\ud -δ, -ε, and -γ1. Significantly high levels of PLC -β1 and -ε\ud were seen in breast cancer tissues in comparison with normal\ud mammary gland tissues. PLC-γ1 however, showed marginally\ud low levels in tumour tissues. No significant difference was\ud seen in the expression of the PLC isozymes in tumours with\ud lymph node metastases. Moderately and poorly differentiated\ud breast tumours (grade 2 and grade 3) had significantly higher\ud levels of PLC-γ1, compared with well differentiated tumours.\ud High levels of PLC-δ were significantly correlated with a\ud shorter disease-free survival. The altered expression of other\ud isozymes had no correlation with the survival. It is concluded\ud that mammary tissues differentially expressed PLC isozymes.\ud These isozymes have certain implications in the disease development\ud and progression, with PLC-δ showing a significant\ud correlation with shorter disease-free survival.