Involvement of human beta-defensin-2 in proliferation of transformed cells of human cervix.
OBJECTIVE
To evaluate the influence of human beta-defensin-2 (hBD-2) on viability and proliferation of cultured human epithelial cells and the patterns of hBD-2 expression in normal tissues and early-stage human cervical neoplasia in the relation to proliferative state of these cells.


METHODS
The influence of recombinant hBD-2 on viability and proliferation of cultured cells of A431 and M-HeLa lines in vitro was performed by MTT-test, 3H-thymidine incorporation and cell counting techniques. Immunohistochemical analysis of expression of hBD-2 and PCNA in tissue samples (10 normal cases (control), 30 carcinomas of the cervix uteri: 15 - squamous cell carcinoma in situ (Stage 0), and 15 squamous cell carcinoma (Stage Ia)) was performed with the use of anti-hBD-2 and anti-PCNA-mAbs, respectively.


RESULTS
We have revealed that hBD-2 significantly stimulated proliferation of A431 and M-HeLa cells in a concentration-dependent manner in the range of 0.1-2 microg/ml, whilst at higher concentrations (> 3-5 microg/ml) it negatively influenced cell viability. The results of immunohistochemical study have shown that malignant transformation of human cervical epithelium is accompanied by the increase of expression of hBD-2 and PCNA. However, the correlative analysis of the expression of the mentioned markers has revealed no relation between them.


CONCLUSIONS
The effect of hBD-2 on viability and proliferation of cultured epithelial cells possesses a concentration-dependent character. Expression of hBD-2 is increased in early-stage cervical carcinoma.
Markeeva
N
N
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine.
Lysovskiy
I
I
Zhuravel
E
E
Soldatkina
M
M
Lyzogubov
V
V
Usenko
V
V
Potapov
V
V
Pogrebnoy
P
P
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D023083:beta-Defensins / Q000378:metabolism* / Q000494:pharmacology
C106641:DEFB4A protein, human; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D023083:beta-Defensins