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Expressions of ATF6, XBP1, and GRP78 in normal tissue, atypical adenomatous hyperplasia, and adenocarcinoma of the lung
- Source :
- Human pathology. 83
- Publication Year :
- 2018
-
Abstract
- Little is known about the association between the atypical adenomatous hyperplasia (AAH)-adenocarcinoma in situ sequence of the lung and endoplasmic reticulum-stress responders such as ATF6, XBP1, and GRP78. Using stored tissues, we examined (i) the percentage of a splicing form (active form) of XBP1 messenger RNA in normal lung tissue (NLT) and adenocarcinoma (ACA; using reverse-transcription polymerase chain reaction); (ii) ATF6 and GRP78 protein expressions in NLT and ACA (using Western blotting analysis); (iii) ATF6, XBP1, and GRP78 protein expressions in NLT, AAH, and ACA, including some adenocarcinoma in situ (using immunohistochemistry); and (iv) the incidence of nuclear translocation of the 3 proteins in these lesions. The percentage of the splicing form of XBP1 messenger RNA showed a borderline difference between NLT and ACA (P = .068). In the Western blotting analysis, the nuclear fractions of ATF6 (including the active form) and GRP78 proteins were higher in ACA than in NLT. In the immunohistochemistry, the values obtained for the incidence of the nuclear translocation of ATF6, XBP1, and GRP78 proteins were as follows, respectively: 13.3%, 2.2%, and 0.5% in low-grade AAH; 37.9%, 2.3%, and 2.2% in high-grade AAH; and 47.2%, 10.6%, and 4.4% in ACA. A significant difference was detected between low-grade AAH and ACA for ATF6. In terms of nuclear translocation, high-grade AAH seemed intermediate between low-grade AAH and ACA. These results support endoplasmic reticulum-stress responses, such as nuclear translocation of these 3 proteins (including their active forms), being in parallel with the progression of the adenoma-carcinoma sequence in the lung.
- Subjects :
- 0301 basic medicine
Male
X-Box Binding Protein 1
Lung Neoplasms
Adenocarcinoma of Lung
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
medicine
Adenocarcinoma of the lung
Humans
Atypical adenomatous hyperplasia
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Aged
Messenger RNA
Hyperplasia
Chemistry
Endoplasmic reticulum
Middle Aged
medicine.disease
Endoplasmic Reticulum Stress
Molecular biology
Activating Transcription Factor 6
Blot
stomatognathic diseases
Protein Transport
030104 developmental biology
030220 oncology & carcinogenesis
RNA splicing
Disease Progression
Immunohistochemistry
Adenocarcinoma
Female
Precancerous Conditions
Subjects
Details
- ISSN :
- 15328392
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Human pathology
- Accession number :
- edsair.doi.dedup.....6e1aa9ac026d962e8e7a23fedf1457ce