Gene expression profiling to identify oncogenic determinants of autocrine human growth hormone in human mammary carcinoma.
We have exploited a discrepancy in the oncogenic potential of autocrine and exogenous human growth hormone (hGH) in an attempt to identify molecules that could potentially be involved in oncogenic transformation of the human mammary epithelial cell. Microarray analysis of 19,000 human genes identified a subset of 305 genes in a human mammary carcinoma cell line that were remarkably different in their response to autocrine and exogenous hGH. Autocrine and exogenous hGH also regulated 167 common genes. Semiquantitative reverse transcription-PCR confirmed differential regulation of genes by either autocrine or exogenous hGH. Functional analysis of one of the identified autocrine hGH-regulated genes, TFF3, determined that its expression is sufficient to support anchorage-independent growth of human mammary carcinoma cells. Small interfering RNA-mediated knockdown of TFF3 concordantly abrogated anchorage-independent growth of mammary carcinoma cells and abrogated the ability of autocrine hGH to stimulate oncogenic transformation of immortalized human mammary epithelial cells. Further functional characterization of the identified subset of specifically autocrine hGH regulated genes will delineate additional novel oncogenes for the human mammary epithelial cell.
Xu
Xiu Qin
XQ
Microarray and Expression Genomics, Genome Institute of Singapore, Republic of Singapore.
Emerald
B Starling
BS
Goh
Eyleen L K
EL
Kannan
Nagarajan
N
Miller
Lance D
LD
Gluckman
Peter D
PD
Liu
Edison T
ET
Lobie
Peter E
PE
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D017931:DNA Primers; D020869:Gene Expression Profiling; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D009077:Mucins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D010455:Peptides; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071165:Trefoil Factor-3
D017931:DNA Primers; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D034741:RNA, Small Interfering; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D019382:Human Growth Hormone