The Expression of Sel1L and Tan-1 in Normal and Neoplastic Cells

Cattaneo, Monica; Orlandi, Rosaria; Ronchini, Chiara; Granelli, P.; Malferrari, Giulia; Ménard, Sylvie; Biunno, Ida

doi:10.1177/172460080001500105

Cited by 20 publications

(15 citation statements)

References 27 publications

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“…1A, panels A.1-A.3). All of these cell lines expressed SEL1L-B and -C transcripts, although at levels lower than SEL1L-A (12). In fact the SEL1L-B and -C signals in Fig.…”

Section: Cloning and Characterization Of Endogenous Sel1l-b And -C-us-mentioning

confidence: 78%

Functional Characterization of Two Secreted SEL1L Isoforms Capable of Exporting Unassembled Substrate

Cattaneo

Lotti

Martino

et al. 2009

Journal of Biological Chemistry

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SEL1L-A, a transmembrane glycoprotein residing in the endoplasmic reticulum (ER), is a component of the ER-associated degradation (ERAD) pathway. Alternative splicing generates two smaller SEL1L isoforms, -B and -C, that lack the SEL1L-A membrane-spanning region but retain some sel-1-like repeats, known to be involved in multi-protein interactions and signal transduction. In this study the functional characteristics of SEL1L-B and -C were investigated in human cell models. We show that these two isoforms are induced upon ER stress and activation of the unfolded protein response, together with SEL1L-A. Using transient transfection experiments (based on wild-type and mutant SEL1L constructs) combined with several biochemical tests we show that SEL1L-B and, more prominently, SEL1L-C are secreted glycoproteins. Although SEL1L-C is in monomeric form, SEL1L-B is engaged in intramolecular/intermolecular disulfide bonds. Both isoforms localize in secretory and degradative cellular compartments and in areas of cell-cell contact. However, whereas SEL1L-B is mainly associated with membranes, SEL1L-C shows the typical intralumenal localization of soluble proteins and is present in intercellular spaces. Furthermore, because of its peroxisomal domain, SEL1L-C localizes to peroxisomes. Both SEL1L-B and -C are involved in sorting and exporting unassembled Ig-s but do not affect two other ERAD substrates, the null Hong Kong variant of ␣ 1 -antitrypsin, and mutant ␣ 1 -AT Z. Overall these findings suggest that SEL1L-B and -C participate to novel molecular pathways that, in parallel with ERAD, contribute to the disposure of misfolded/unfolded or orphan proteins through degradation or secretion.

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“…1A, panels A.1-A.3). All of these cell lines expressed SEL1L-B and -C transcripts, although at levels lower than SEL1L-A (12). In fact the SEL1L-B and -C signals in Fig.…”

Section: Cloning and Characterization Of Endogenous Sel1l-b And -C-us-mentioning

confidence: 78%

Functional Characterization of Two Secreted SEL1L Isoforms Capable of Exporting Unassembled Substrate

Cattaneo

Lotti

Martino

et al. 2009

Journal of Biological Chemistry

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“…SEL1L has been reported as highly expressed in human developing and normal adult pancreas with much lower levels detected in other tissues (Biunno et al, 1997;Donoviel et al, 1998;Harada et al, 1999;Cattaneo et al, 2000). SEL1L has been also found downregulated or completely repressed in a proportion of primary adenocarcinomas of the pancreas (Biunno et al, 1997;Donoviel et al, 1998).…”

Section: Introductionmentioning

confidence: 97%

SEL1L expression in pancreatic adenocarcinoma parallels SMAD4 expression and delays tumor growth in vitro and in vivo

et al. 2003

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Recent data suggest that SEL1L may play an important role in pancreatic carcinoma, similar to breast cancer, where the expression of SEL1L has been associated with a reduction in both proliferative activity in vitro and clinical tumor aggressiveness. To investigate this possibility, we examined the expression of Sel1L in a series of primary pancreatic carcinomas by immunohistochemistry and characterized the effects of Sel1L overexpression both in vitro and in vivo. In 74 pancreatic cancers analysed, 36% lacked Sel1L expression, although there was no significant correlation between the expression of Sel1L and any clinicopathologic parameter, including survival. However, immunohistochemical reactivity for Sel1L and Dpc4/ Smad4 was concordant in 69% of cases (v 2 test Po0.004). Overexpression of SEL1L in stably transfected pancreatic cancer cells caused both a decrease in clonogenicity and anchorage-independent growth as well as a significant increase in the levels of activin A and SMAD4. When implanted in nude mice, Suit-2-SEL1L-overexpressing clones displayed a considerably reduced rate of tumor growth. Thus, it can be hypothesized that Sel1L plays an important function in the growth and aggressiveness of pancreatic carcinoma. Moreover, our data provide evidence that SEL1L has an impact on the expression of genes involved in regulation of cellular growth, possibly through the TGF-b signaling pathway.

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“…It has been reported that SEL1L expression decreases breast cancer cell aggressiveness in vivo and in vitro and that down-regulation correlates with poor prognosis (1). Generally, SEL1L is abundantly expressed only in the pancreas (2,3) and more specifically in the acini and islets of Langerhans (4,5). However, 36% of primary pancreatic cancers do not express the gene, and a significant correlation was found with Dpc4.…”

Section: Introductionmentioning

confidence: 99%

SEL1L and Squamous Cell Carcinoma of the Esophagus

Granelli

Cattaneo

Ferrero

et al. 2004

Clinical Cancer Research

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The gene SEL1L is involved both in human breast and pancreatic cancer progression. It is located on 14q24.3-31, a region known to be lost in invasive cancer of the esophagus. We aimed to assess whether SEL1L could become a useful biomarker for this cancer. We assessed SEL1L mRNA and protein expression in 35 patients and found it to be weak in low-grade and strong in high-grade dysplasia. Although the majority of cancer patients showed differential expression (mRNA and protein) of SEL1L, in five cases it was completely absent; these patients had the worst outcomes. SEL1L immunoreactivity was negative in normal tissue samples from five patients with mild esophagitis as well as in normal mucosa adjacent to the tumor. We hypothesize that SEL1L could influence those cellular changes that mediate the transition from a normal mucosa to a neoplastic lesion and may help in the identification of those patients at higher risk of developing this cancer. The specific impact of SEL1L in esophageal cancer needs further investigation.

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The Expression of Sel1L and Tan-1 in Normal and Neoplastic Cells

Cited by 20 publications

References 27 publications

Functional Characterization of Two Secreted SEL1L Isoforms Capable of Exporting Unassembled Substrate

Functional Characterization of Two Secreted SEL1L Isoforms Capable of Exporting Unassembled Substrate

SEL1L expression in pancreatic adenocarcinoma parallels SMAD4 expression and delays tumor growth in vitro and in vivo

SEL1L and Squamous Cell Carcinoma of the Esophagus

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