Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa.
OBJECTIVE
To analyze possible relationships between CA IX/CA XII and pVHL expression in normal and neoplastic colorectal mucosa.


METHODS
Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA IX, CA XII and pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGF as an indicator of hypoxia that uncouples the pVHL control.


RESULTS
Tumor tissues were associated with a borderline increase of CA IX staining signal and slight but significant decrease of CA XII immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL and CA IX/CA XII proteins as well as between VEGF and CA9 mRNAs, but the tumor-associated changes in mRNA levels of VEGF and CA12 showed a significant inverse relationship.


CONCLUSIONS
Our results indicate that CA9 and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA IX/CA XII and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA IX/CA XII in colorectal tumors seems rather complex and is not evident merely at the expression levels.
Kivela
Antti-J
AJ
Department of Anatomy and Cell Biology, University of Oulu, Finland.
Parkkila
Seppo
S
Saarnio
Juha
J
Karttunen
Tuomo-J
TJ
Kivela
Jyrki
J
Parkkila
Anna-Kaisa
AK
Bartosova
Maria
M
Mucha
Vojtech
V
Novak
Michal
M
Waheed
Abdul
A
Sly
William-S
WS
Rajaniemi
Hannu
H
Pastorekova
Silvia
S
Pastorek
Jaromir
J
D000951:Antigens, Neoplasm / Q000235:genetics*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics*; D003106:Colon / Q000378:metabolism / Q000503:physiopathology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D000951:Antigens, Neoplasm; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII; C497446:VHL protein, human