Abstract
In human cancer cells, BAG3 protein is known to sustain cell survival. Here, for the first time, we demonstrate the expression of BAG3 protein both in equine sarcoids in vivo and in EqS04b cells, a sarcoid-derived fully transformed cell line harbouring bovine papilloma virus (BPV)-1 genome. Evidence of a possible involvement of BAG3 in equine sarcoid carcinogenesis was obtained by immunohistochemistry analysis of tumour samples. We found that most tumour samples stained positive for BAG3, even though to a different grade, while normal dermal fibroblasts from healthy horses displayed very weak staining pattern for BAG3 expression. By siRNA technology, we demonstrate in EqS04b the role of BAG3 in counteracting basal as well as chemical-triggered pro-death signals. BAG3 down-modulation was indeed shown to promote cell death and cell cycle arrest in G0/G1. In addition, we found that BAG3 silencing sensitized EqS04b cells to phenethylisothiocyanate (PEITC), a promising cancer chemopreventive/chemotherapeutic agent present in edible cruciferous vegetables. Notably, such a pro-survival role of BAG3 was less marked in E. Derm cells, an equine BPV-negative fibroblast cell line taken as a normal counterpart. Altogether our findings might suggest a mutual cooperation between BAG3 and viral oncoproteins to sustain cell survival.
Highlights
Sarcoids are the most common dermatological neoplasms affecting equids [1]
Normal dermal fibroblasts derived from healthy horses displayed very weak staining patterns for BAG family molecular chaperone regulator 3 (BAG3) expression (Figure 1b)
For the first time, we demonstrate that BAG3 protein is expressed in a subset of naturally occurring equine sarcoids, expressing bovine papillomavirus (BPV)-1 genome, and that it sensitizes equine sarcoid-derived cells to PEITC, a promising cancer chemopreventive/ chemotherapeutic agent present in edible cruciferous vegetables [27]
Summary
Sarcoids are the most common dermatological neoplasms affecting equids [1]. These neoplasms are benign lesions of fibroblastic origin, that often occur at sites of previous injury or scarring; they are locally aggressive and invasive, but rarely metastasize [2]. The sarcoids are characterized by dermal proliferation of fibroblasts, forming whorls and epidermal hyperplasia. The pathology of this equine neoplasm is not completely understood, bovine papillomavirus (BPV) is considered to be the etiological agent. BPV type 1 and type 2 (BPV-1/-2) are non-enveloped, double stranded, DNA viruses, which commonly infect their natural host. BPV-1, and less commonly BPV-2, have been detected in sarcoids in different geographic areas of the world [3]. The major transforming product of BPV is E5, a very small membrane-associated protein with potent
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