Sarcoglycans in the Normal and Pathological Breast Tissue of Humans: An Immunohistochemical and Molecular Study

Abstract

The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant.

Expression of Sarcoglycans in the Human Cerebral Cortex: An Immunohistochemical and Molecular Study

“…present in other non-muscular districts, e.g. breast epithelium [Arco et al, 2011] or respiratory, intestinal and urinary epithelium (data not shown). Therefore, it can be suggested that the SG complex is not muscle specific but rather ubiquitously present in several tissue regions in which, however, its role may differ depending on the different interactions.…”

“…Cai et al [2007] studied SGC in Schwann cells and its role in the stability of peripheral nerve myelin. Studies on SGs are inconsistent: in some SGs were only noted in striated and smooth muscles, whereas other studies also showed their presence in non-muscle cells [Ettinger et al, 1997;Arco et al, 2011]. Recently, SGs have also been ascribed a role in CNS function and CNS disease [Zimprich et al, 2001].…”

Sarcoglycan Complex in Human Normal and Pathological Prostatic Tissue: An Immunohistochemical and RT‐PCR Study

“…Our data show the presence of all SGs in normal prostatic tissue, and as such are in contrast with previous reports which hypothesized that α‐ and γ‐SG are expressed in skeletal and cardiac muscle only (Roberds et al, ; Lim et al, ; Noguchi et al, ; Nigro et al, ; Liu et al, ), suggesting that the SGC is not muscle‐specific. Previously, our preliminary data on epithelial cells of many districts (unpublished data) and on epithelial cells of breast have shown that all SGs are clearly detectable, evidencing a wider distribution of the SGC (Arco et al, ).…”

“…In the past, it was shown that mutations in any SG cause Limb-Girdle Muscular Dystrophy (Campbell, 1995) provoking, interestingly, dysphagia, vomiting and acute digestive dilatations (Barhon et al, 1998). In our opinion, to understand the real role and function of SGs, it is necessary to study these proteins, not only in normal, but also in pathological conditions, as we previously did, in breast epithelium (Arco et al, 2012). For this reason, we have analyzed all SGs also in human samples of prostatic glandular epithelium from patients affected by benign prostatic hyperplasia and prostatic adenocarcinoma.…”

Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients

“…Data about their role in cancer progression are scarce, consisting of a few reports on different types of cancer. Downregulation of SGCG was detected in NSCLC [49] and breast cancer [50], while Saraon et al [51] revealed elevation of PROS1 in high grade aggressive prostate cancer. Contrary to this, PROS1 seems to be downregulated in anaplastic meningiomas [52].…”