Chlamydia trachomatis modulates expression of tumor suppressor gene caveolin-1 and oncogene C-myc in the transformation zone of non-neoplastic cervical tissue.
OBJECTIVE
The obligate intracellular bacterium Chlamydia trachomatis is frequently found in association with benign proliferative, pre-neoplastic and malignant changes in cervical epithelium. The present study addresses the possible role of C. trachomatis infection of the uterine cervix in modulating human cancer gene expression.


METHODS
RNA was extracted from both C. trachomatis infected and non-infected human fibroblast cultures treated with ITFgamma. The extracted RNA was used for cDNA microarrays carrying 33,000 human genes to detect abnormal gene expression induced by Chlamydia. Forty specimens of cervix dissected from the transformation zone had previously tested negative for HPV and positive for C. trachomatis by standard DNA PCR (20). These samples were subjected to RT-PCR to detect the expression of the abnormal genes induced by Chlamydia infection.


RESULTS
The ITFgamma-induced, non-replicative Chlamydia-infected fibroblast cultures showed significant modulation of gene expression. The cultures showed a 2-fold decrease in the expression of the gene coding for the tumor suppressor caveolin-1, and increased expression of the oncogene C-myc, a promoter of cervical carcinogenesis. In tissues from the Chlamydia-infected cervical transformation zone, real-time RT-PCR demonstrated a highly significant average 4.7-fold reduction of caveolin-1 mRNA (P < or = 0.0001) and an average 2.1-fold increase in C-myc (P < 0.05).


CONCLUSIONS
Human ITFgamma-treated fibroblasts as well as non-neoplastic cervical tissues responded to C. trachomatis with a strong down-regulation of caveolin-1 mRNA and a light up-regulation of C-myc mRNA. These changes were independent of the HPV high-risk types. This study reveals possible mechanisms by which C. trachomatis infection may contribute to neoplastic changes in the transformation of uterine cervix. These possible mechanisms require further evaluation.
Schlott
Thilo
T
Department of Pathology, Georg August University, Robert-Koch-Str 40, D-37075 Goettingen, Germany. tschlott@med.uni-goettingen.de
Eiffert
Helmut
H
Bohne
Wolfgang
W
Landgrebe
Jobst
J
Brunner
Edgar
E
Spielbauer
Bettina
B
Knight
Bryan
B
D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002584:Cervix Uteri / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D002690:Chlamydia Infections / Q000150:complications / Q000235:genetics / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000254:growth & development / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000382:microbiology*
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D007371:Interferon-gamma