Increased expression of high mobility group A proteins in lung cancer.
High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. In this work, the expression of HMGA 1 and 2 in 152 lung carcinomas of mainly non-small-cell histological type has been studied by immunohistochemistry in order to evaluate their feasibility as lung cancer markers. In 17 lung cancer cases, the related bronchial epithelial changes were also studied for HMGA1 and 2 expression. RNA expression of HMGA1a and b isoforms and of HMGA2 was determined by real-time semi-quantitative RT-PCR in 23 lung carcinomas. High expression of HMGA1 and HMGA2 at both mRNA and protein levels was detected in lung carcinomas, compared with normal lung tissue. Nuclear immunostaining for HMGA1 and 2 proteins also occurred in hyperplastic, metaplastic, and dysplastic bronchial epithelium. Increased nuclear expression of HMGA1 and 2 correlated with poor survival (for adenocarcinomas, HMGA1, p=0.006; HMGA2, p=0.05). While the expression of HMGA2 was significantly associated with cell proliferation (p=0.008), HMGA1 expression did not show any association with proliferation or apoptotic index. Sequencing of HMGA2 transcripts from tumours with very high expression showed a normal full-length transcript. As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, they may provide useful markers for lung cancer diagnosis and prognosis.
Sarhadi
V K
VK
Department of Occupational Medicine, Finnish Institute of Occupational Health, Helsinki, Finland.
Wikman
H
H
Salmenkivi
K
K
Kuosma
E
E
Sioris
T
T
Salo
J
J
Karjalainen
A
A
Knuutila
S
S
Anttila
S
S
D000368:Aged; D017209:Apoptosis / Q000502:physiology; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D005260:Female; D024003:HMGA Proteins / Q000032:analysis*; D025741:HMGA1a Protein / Q000032:analysis; D025742:HMGA1b Protein / Q000032:analysis; D025743:HMGA2 Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D046888:Tissue Array Analysis / Q000379:methods
D024003:HMGA Proteins; D025743:HMGA2 Protein; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D025742:HMGA1b Protein; D025741:HMGA1a Protein