TY - JOUR

T1 - Identification of genes differentially expressed in testes containing carcinoma in situ

AU - Hoei-Hansen, C. E.

AU - Nielsen, J. E.

AU - Almstrup, K.

AU - Hansen, M. A.

AU - Skakkebaek, N. E.

AU - Rajpert-DeMeyts, E.

AU - Leffers, H.

N1 - Funding Information: We wish to thank Marlene Dalgaard and Brian Vendelbo Hansen for excellent technical assistance. The study was supported by grants from The Danish Cancer Society, The Svend Andersen Foundation and The Danish Medical Research Council.

PY - 2004/6

Y1 - 2004/6

N2 - Virtually all testicular germ cell tumours originate from a common precursor, the carcinoma in situ (CIS) cell. The precise nature of the molecular mechanisms leading to CIS remains largely unknown. We performed the first systematic analysis of gene expression in testis with CIS compared to normal testis by the differential display (DDRT-PCR) method, with subsequent analysis by RT-PCR and in situ hybridization (ISH). In tissue containing CIS we identified overexpression of 28 mRNA, some previously reported in CIS and a number of genes not previously described in germ cell neoplasia, including the novel expressed sequence tag (EST) OIC1 (Overexpressed In CIS). The genes could be grouped functionally into genes involved in cell growth, proliferation, differentiation, immunological response, and genes with unknown biological function. Examples of overexpressed genes are SFRP1 that is involved in Wnt signalling and IGFBP6, which is of importance for fetal growth and inhibits cell growth through insulin-like growth factor-II. ISH analysis showed that both mRNA were localized to CIS cells. The results of our search for differentially expressed genes in CIS demonstrated a number of genes linked to testicular development (e.g. DCN, IGFBP6, SFRP1, SALL1), supporting our hypothesis that the origin of CIS is probably associated with disturbances of the fetal development of the testis.

AB - Virtually all testicular germ cell tumours originate from a common precursor, the carcinoma in situ (CIS) cell. The precise nature of the molecular mechanisms leading to CIS remains largely unknown. We performed the first systematic analysis of gene expression in testis with CIS compared to normal testis by the differential display (DDRT-PCR) method, with subsequent analysis by RT-PCR and in situ hybridization (ISH). In tissue containing CIS we identified overexpression of 28 mRNA, some previously reported in CIS and a number of genes not previously described in germ cell neoplasia, including the novel expressed sequence tag (EST) OIC1 (Overexpressed In CIS). The genes could be grouped functionally into genes involved in cell growth, proliferation, differentiation, immunological response, and genes with unknown biological function. Examples of overexpressed genes are SFRP1 that is involved in Wnt signalling and IGFBP6, which is of importance for fetal growth and inhibits cell growth through insulin-like growth factor-II. ISH analysis showed that both mRNA were localized to CIS cells. The results of our search for differentially expressed genes in CIS demonstrated a number of genes linked to testicular development (e.g. DCN, IGFBP6, SFRP1, SALL1), supporting our hypothesis that the origin of CIS is probably associated with disturbances of the fetal development of the testis.

KW - Carcinoma in situ

KW - Differential display

KW - IGFBP-6

KW - SFRP1

KW - Testicular cancer

UR - http://www.scopus.com/inward/record.url?scp=2642570002&partnerID=8YFLogxK

U2 - 10.1093/molehr/gah059

DO - 10.1093/molehr/gah059

M3 - Journal article

C2 - 15123780

AN - SCOPUS:2642570002

VL - 10

SP - 423

EP - 431

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

SN - 1360-9947

IS - 6

ER -