The possible modulation of p63 and other genes in prostate tumorigenesis
Prostate cancer (PCa) affects males in Malaysia, where in Peninsular Malaysia prostate cancer was the sixth most frequent cancer in males and accounted for 6.4% of the total cancers in males for the year 2003. In Sarawak, prostate cancer ranked eighth among the most frequent cancer occurrence in...
Saved in:
Main Author: | |
---|---|
Format: | Thesis |
Language: | English |
Published: |
2007
|
Subjects: | |
Online Access: | http://ir.unimas.my/id/eprint/32678/1/Nguok%20%28ft%29.pdf |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
my-unimas-ir.32678 |
---|---|
record_format |
uketd_dc |
spelling |
my-unimas-ir.326782023-08-10T02:24:08Z The possible modulation of p63 and other genes in prostate tumorigenesis 2007 Su, Nguok Ngie RC Internal medicine RC0254 Neoplasms. Tumors. Oncology (including Cancer) Prostate cancer (PCa) affects males in Malaysia, where in Peninsular Malaysia prostate cancer was the sixth most frequent cancer in males and accounted for 6.4% of the total cancers in males for the year 2003. In Sarawak, prostate cancer ranked eighth among the most frequent cancer occurrence in males with a rate of 3.4% of the total cancers in males for the year 1996-2000. Mice knockout for p63 have exhibited developmental defects such as abnormal skin and absence of hair follicles, prostate, breast, teeth and mammary glands. Mutation of p63 in human resulted in the ectrodactyly, ectodermal dysplasia and facial clefts (EEC) syndrome. Mutational analyses have revealed heterozygous mutation of p63 in colon (DLD1) and ovarian (SKOV3) cancer cell lines. Studies have shown that the p63 gene was selectively expressed in basal cells of normal, benign prostatic hyperplasia (BPH), prostatic epithelial stem cells and preneoplastic prostatic tissue Although indirect evidences from literature have implicated possible role(s) of p63 in prostate cancer, its actual involvement in the carcinogenesis of this cancer has yet been established. Furthermore, few studies have been done so far to delineate the molecular and genetic mechanisms that pertain to the predisposition and progression of prostate cancer. In this study, mutation analysis of p63 on prostate cancer cell line (PC-3), PCa biopsy and BPH biopsies have been performed. However, no mutation was detected in PC-3, CaP and BPH biopsies. Expression studies on various isoforms of p63 were performed on normal human prostate tissue, PC-3, clinically local prostate cancer and benign prostatic hyperplasia using RT-PCR. In addition, we report new data on the identification of differentially expressed III genes using gene expression profile analysis of the PC-3 cell line. The gene expression analysis data revealed a total of 673 downregulated genes and 240 upregulated genes. Sixteen transcripts were chosen from the differentially expressed genes for RT-PCR verification assay. The respective genes were HAT1, GAGE4, RPL30, BMP6, VIM, LOX, GNAll, MYBPC2, CASP5, FHL20, KLK10, A20, ANXA2, MYBPC3, SCGB2A2 and TNNT3. The majority of them concurred with existing literature (RPL30, FHL20, ANXA2, KLK10, BMP6, VIM), whereas some the differentially expressed genes represented the novel findings (GAGE4, MYBPC2, CASP5, A20, GNAll). The microarray results obtained from this study were based on only one sample. Therefore this is a preliminary result of gene expression for prostate carcinogenesis. In future, this preliminary microarray result can be strengthened by performing more microarray tests on more samples or through RT-PCR assays. It would be of interest to identify the roles of more candidate genes in the prostate carcinogenesis pathways. It is also necessary in future studies to identify whether alterations of mRNA levels to these genes correspond to the changes in protein levels in prostate cancer. Universiti Malaysia Sarawak (UNIMAS) 2007 Thesis http://ir.unimas.my/id/eprint/32678/ http://ir.unimas.my/id/eprint/32678/1/Nguok%20%28ft%29.pdf text en validuser masters Universiti Malaysia Sarawak (UNIMAS) Faculty of Resource Science and Technology |
institution |
Universiti Malaysia Sarawak |
collection |
UNIMAS Institutional Repository |
language |
English |
topic |
RC Internal medicine RC Internal medicine |
spellingShingle |
RC Internal medicine RC Internal medicine Su, Nguok Ngie The possible modulation of p63 and other genes in prostate tumorigenesis |
description |
Prostate cancer (PCa) affects males in Malaysia, where in Peninsular Malaysia prostate
cancer was the sixth most frequent cancer in males and accounted for 6.4% of the total
cancers in males for the year 2003. In Sarawak, prostate cancer ranked eighth among the
most frequent cancer occurrence in males with a rate of 3.4% of the total cancers in males
for the year 1996-2000. Mice knockout for p63 have exhibited developmental defects such as
abnormal skin and absence of hair follicles, prostate, breast, teeth and mammary glands.
Mutation of p63 in human resulted in the ectrodactyly, ectodermal dysplasia and facial
clefts (EEC) syndrome. Mutational analyses have revealed heterozygous mutation of p63 in
colon (DLD1) and ovarian (SKOV3) cancer cell lines. Studies have shown that the p63 gene
was selectively expressed in basal cells of normal, benign prostatic hyperplasia (BPH),
prostatic epithelial stem cells and preneoplastic prostatic tissue Although indirect
evidences from literature have implicated possible role(s) of p63 in prostate cancer, its
actual involvement in the carcinogenesis of this cancer has yet been established.
Furthermore, few studies have been done so far to delineate the molecular and genetic
mechanisms that pertain to the predisposition and progression of prostate cancer. In this
study, mutation analysis of p63 on prostate cancer cell line (PC-3), PCa biopsy and BPH
biopsies have been performed. However, no mutation was detected in PC-3, CaP and BPH
biopsies. Expression studies on various isoforms of p63 were performed on normal human
prostate tissue, PC-3, clinically local prostate cancer and benign prostatic hyperplasia using
RT-PCR. In addition, we report new data on the identification of differentially expressed
III
genes using gene expression profile analysis of the PC-3 cell line. The gene expression
analysis data revealed a total of 673 downregulated genes and 240 upregulated genes.
Sixteen transcripts were chosen from the differentially expressed genes for RT-PCR
verification assay. The respective genes were HAT1, GAGE4, RPL30, BMP6, VIM, LOX,
GNAll, MYBPC2, CASP5, FHL20, KLK10, A20, ANXA2, MYBPC3, SCGB2A2 and TNNT3.
The majority of them concurred with existing literature (RPL30, FHL20, ANXA2, KLK10,
BMP6, VIM), whereas some the differentially expressed genes represented the novel
findings (GAGE4, MYBPC2, CASP5, A20, GNAll). The microarray results obtained from
this study were based on only one sample. Therefore this is a preliminary result of gene
expression for prostate carcinogenesis. In future, this preliminary microarray result can be
strengthened by performing more microarray tests on more samples or through RT-PCR
assays. It would be of interest to identify the roles of more candidate genes in the prostate
carcinogenesis pathways. It is also necessary in future studies to identify whether
alterations of mRNA levels to these genes correspond to the changes in protein levels in
prostate cancer. |
format |
Thesis |
qualification_level |
Master's degree |
author |
Su, Nguok Ngie |
author_facet |
Su, Nguok Ngie |
author_sort |
Su, Nguok Ngie |
title |
The possible modulation of p63 and other genes in prostate tumorigenesis |
title_short |
The possible modulation of p63 and other genes in prostate tumorigenesis |
title_full |
The possible modulation of p63 and other genes in prostate tumorigenesis |
title_fullStr |
The possible modulation of p63 and other genes in prostate tumorigenesis |
title_full_unstemmed |
The possible modulation of p63 and other genes in prostate tumorigenesis |
title_sort |
possible modulation of p63 and other genes in prostate tumorigenesis |
granting_institution |
Universiti Malaysia Sarawak (UNIMAS) |
granting_department |
Faculty of Resource Science and Technology |
publishDate |
2007 |
url |
http://ir.unimas.my/id/eprint/32678/1/Nguok%20%28ft%29.pdf |
_version_ |
1783728418709307392 |