Overexpression of RB1 transcript is significantly correlated with 13q14 allelic imbalance in colorectal carcinomas.
RB1 gene expression has been reported to be upregulated in colorectal carcinomas (CRC) at both the mRNA and protein levels when compared to normal colonic mucosa. However, allelic loss at the genomic level has been detected in CRC with widely differing frequencies ranging from 11.5% to 50%. To determine whether there is indeed a correlation between RB1 allelic imbalance (AI) and expression, a consecutive series of 55 CRC from Singapore patients were analysed by microsatellite analysis, real-time RT-PCR and immunohistochemistry. Microsatellite analysis using 3 RB1 intragenic microsatellite markers and 2 markers flanking RB1 detected AI in 32.7% (18/55) of the cases, in at least 1 locus. The highest AI frequency (22.9%) was observed at the microsatellite marker D13S137 (Cu13), which maps 5 cM distal to RB1. AI was present in both early and late Dukes stages. Real-time RT-PCR revealed that all 40 cases analysed expressed RB1 mRNA, with mRNA overexpression in 37.5% (15/40) and pRB protein expression in 88.2% (30/34) of cases. Notably, a statistically significant correlation was found between AI of RB1 and mRNA overexpression of RB1 (p < 0.001, Fishers exact test). These findings provide evidence that despite AI, RB1 expression is not abrogated. Thus, our data suggests that RB1 may play a role in colorectal tumorigenesis through functional regulation of the transcript and protein rather than through its tumour suppressor role by gene inactivation.
Lai
Poh-San
PS
Department of Paediatrics, National University of Singapore, Singapore.
Cheah
Peh Yean
PY
Kadam
Priya
P
Chua
Constance Li-Ming
CL
Lie
Daniel Khun Hong
DK
Li
Hui-Hua
HH
Eu
Kong-Weng
KW
Seow-Choen
Francis
F
Lee
Ann Siew-Gek
AS
D000368:Aged; D022981:Allelic Imbalance; D002882:Chromosomes, Human, Pair 13; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation
D016160:Retinoblastoma Protein