Human Cytochrome P450 2W1 Is Not Expressed in Adrenal Cortex and Is Only Rarely Expressed in Adrenocortical Carcinomas.
Human cytochome P450 2W1 (CYP2W1) enzyme is expressed in fetal colon and in colon tumors. The level of expression is higher in colon metastases than in the parent tumors and the enzyme is a possible drug target for treatment of colorectal cancer, as demonstrated in mouse xenograft studies. A previous study published in this journal reported that CYP2W1 is highly expressed in normal and transformed adrenal tissue. However, adrenal expression of CYP2W1 protein was not seen in previous studies in our research group. To clarify this inconsistency, we have used qRT-PCR and Western blotting with CYP2W1-specific antibodies to probe a panel of 27 adrenocortical carcinomas and 35 normal adrenal cortex samples. CYP2W1 mRNA expression is seen in all samples. However, significant CYP2W1 protein expression was found in only one tumor sample (a testosterone-producing adrenocortical carcinoma) and not in any normal tissue. Differences in the specificity of the CYP2W1 antibodies used in the two studies may explain the apparent discrepancy. We conclude that normal adrenal tissue lacks P450 2W1 enzyme expression; also, adrenocortical carcinomas generally do not express the enzyme. This information thus underline the colon cancer specificity of CYP2W1 enzyme expression and has implications for the development of anti-colon cancer therapies based on CYP2W1 as a drug target, since 2W1-dependent bioactivation of prodrugs for CYP2W1 will not take place in normal adrenal tissue or other non-transformed tissues.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Paola
P
Nolé
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Britt
B
Duijndam
Department of Oncology-Pathology, Karolinska Institutet, and Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
Adam
A
Stenman
Department of Oncology-Pathology, Karolinska Institutet, and Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
C Christofer
CC
Juhlin
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Mikael
M
Kozyra
Department of Oncology-Pathology, Karolinska Institutet, and Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
Catharina
C
Larsson
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Magnus
M
Ingelman-Sundberg
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Inger
http://orcid.org/0000-0001-6646-4551
I
Johansson
D000302:Adrenal Cortex / Q000166:cytology / Q000201:enzymology*; D000306:Adrenal Cortex Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015153:Blotting, Western; D000072467:Cytochrome P450 Family 2 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; C509336:CYP2W1 protein, human; D000072467:Cytochrome P450 Family 2