Aberrant HOXC expression accompanies the malignant phenotype in human prostate.
Dysregulation of HOX gene expression has been implicated as a factor in malignancies for a number of years. However, no consensus has emerged regarding specific causative genes. Using a degenerate reverse transcription-PCR technique, we show up-regulation of genes from the HOXC cluster in malignant prostate cell lines and lymph node metastases. When relative expression levels of the four HOX clusters were examined, lymph node metastases and cell lines derived from lymph node metastases exhibited very similar patterns, patterns distinct from those in benign cells or malignant cell lines derived from other tumor sites. Specific reverse transcription-PCR for HOXC4, HOXC5, HOXC6, and HOXC8 confirmed overexpression of these genes in malignant cell lines and lymph node metastases. Laser capture microdissection and examination of paired tumor/normal prostate epithelial cells also indicated overexpression of these HOXC genes in primary tumor cells. Our data indicate a possible link between expression of HOXC genes and malignancy in prostate cells. Overexpression of HOXC8 in LNCaP prostate cancer cells suppressed transactivation by androgen receptors. We speculate that HOXC overexpression may predispose tumor cells to androgen independence by necessitating adaptation to diminished androgen signaling.
Miller
Gary J
GJ
Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Miller
Heidi L
HL
van Bokhoven
Adrie
A
Lambert
James R
JR
Werahera
Priya N
PN
Schirripa
Osvaldo
O
Lucia
M Scott
MS
Nordeen
Steven K
SK
D000728:Androgens / Q000502:physiology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000728:Androgens; C098691:HOXC4 protein, human; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; C490904:Hoxc4 protein, mouse; C080041:Hoxc6 protein, mouse