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ALTERATIONS OF TRANSFORMING GROWTH FACTOR‐b PATHWAY IN CERVICAL CANCER
Author(s) -
DiazChavez Jose De La Luz,
HernandezPando Rogelio,
Lambert Paul,
Gariglio Patricio
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a31-c
Subject(s) - carcinogenesis , oncogene , biology , transforming growth factor , estrogen , endocrinology , tgf alpha , medicine , cancer research , cell cycle , growth factor , cancer , receptor
Cervical cancer is a multistep process initiated by “high risk” human papillomaviruses, most commonly HPV16. The infection per se is, however, not sufficient to induce malignant conversion. Transforming Growth Factor β(TGF‐β) inhibits epithelial proliferation and altered expression of TGF‐β or its receptors may be important in carcinogenesis. To examine the expression of TGF‐β2 and TGF‐βRII we used in situ RT‐PCR, real‐time PCR and immunohistochemistry in transgenic mice expressing the oncogene E7 of HPV16 under control of the human Keratin‐14 promoter (K14‐E7 mice) and nontransgenic control mice (Nt) treated for 6 months with slow release pellets of 17β‐estradiol. Estrogen‐induced carcinogenesis was accompanied by an increase in the incidence and distribution of proliferating cells solely within the cervical epithelium of K14‐E7 mice. TGF‐β2 mRNA and protein levels increased in K14‐E7 mice as compared with Nt mice and further increased after hormone‐treatment in both Nt and K14‐E7 mice. In contrast, TGF‐βRII mRNA and protein levels decreased in K14‐E7 mice as compared with Nt mice and these levels were further decreased after hormone treatment in K14‐E7 mice. These results suggest that estrogen‐induced neoplastic transformation of the cervix in K14‐E7 mice may be related to an elevation of TGF‐β2 and a reduction of TGF‐βRII expression that may lead to loss of cell cycle control.