Abstract
The observation that galectin-7 (gal-7) is specifically expressed in mammary myoepithelial (basal) cells prompted us to investigate whether this protein is expressed in the basal cells of other tissues. Given that breast and prostate cancer have remarkable underlying biological similarities and given the important roles of basal cells in prostate cancer, we examined the expression patterns and role of gal-7 in human prostate cancer. Using tissue microarray, we found that although gal-7 is readily expressed in basal cells in normal prostate tissue, it is downregulated in prostate cancer (PCa) cells. De novo expression of gal-7 in prostate cancer cells increases their sensitivity to apoptosis in response to etoposide and cisplatin. The assessment of a carbohydrate-recognition domain (CRD)-defective mutant form of gal-7 (R7S) showed that the ability of this protein to modulate apoptosis was independent of its CRD activity. This activity was also independent of its ability to translocate to the mitochondrial and nuclear compartments. However, CRD activity was necessary to inhibit the invasive behaviors of prostate cancer cells. In vivo, gal-7 overexpression in PCa cells led to a modest yet significant reduction in tumor size, while its CRD-defective mutant form significantly increased tumor growth compared to controls. Taken together, these results suggest that although de novo expression of gal-7 may be an interesting means of increasing the tumorigenic phenotypes of PCa cells, alterations in the CRD activity of this protein drive a phenotypic switch in its role in PCa cells. This CRD-independent activity represents a paradigm shift in our understanding of the functions of galectin. The R74S model will be useful to distinguish CRD-dependent and CRD-independent functions of gal-7 in cancer progression.
Highlights
Galectin-7 is a p53-induced gene that is mainly expressed in stratified epithelial cells [1, 2]
The low expression in PCa tissues was consistent with expression patterns found during our investigations of gal-7 expression at the mRNA and protein levels in the most common prostate cancer cell line models
Immunoblotting experiments demonstrated that none of these cell lines expressed readily detectable levels of gal-7; mRNA was expressed at a low but detectable level in PC3 cells (Fig 1). These results showed that gal-7 is readily expressed in basal cells within normal prostate tissue, it is completely absent in prostate cancer cells
Summary
Galectin-7 (gal-7) is a p53-induced gene that is mainly expressed in stratified epithelial cells [1, 2]. As a number of studies have shown, gal-7, similar to other galectins, plays a dual role in cancer and can have a protective role in certain cases, most notably by increasing the sensitivity of cancer cells to pro-apoptotic stimuli and by reducing cell growth and angiogenesis. These activities have been relatively well documented in gastric, urothelial, and colon cancers, as well as in cervical squamous carcinoma [6, 14, 15]. Given the increasing popularity of epigenetic treatments for cancer, it is imperative to determine whether gal-7 has a pro- or anti-tumor function in any given type of cancer, most notably those of epithelial origin
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