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Anti‐proliferative effect of retinoids and interferon‐α‐2a on vaginal cell lines derived from squamous intra‐epithelial lesions
Author(s) -
Hietanen Sakari,
Auvinen Eeva,
Syrjänen Kari,
Syrjänen Stina
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19981029)78:3<338::aid-ijc14>3.0.co;2-2
Subject(s) - cell culture , cell growth , retinoic acid , retinoid , interferon , growth inhibition , endocrinology , medicine , biology , epithelium , microbiology and biotechnology , chemistry , cancer research , immunology , biochemistry , genetics
A panel of retinoids (all‐ trans‐, 13‐ cis‐, 19‐ cis retinoic acid and acitretin), and interferon‐α‐2a was tested for the capacity to modulate the proliferation of UT‐DEC‐1 (HPV‐33‐positive) and UT‐DEC‐2 (HPV‐16‐positive) cell lines derived from vaginal intra‐epithelial neoplasias (VAIN). At concentrations 10 −6 to 10 −8 M, all retinoids inhibited the growth of early‐passage UT‐DEC cell lines, but also of normal vaginal keratinocytes and fibroblasts. The inhibition was significantly reduced in late‐passage UT‐DEC cells. The effect on proliferation was essentially equal for all retinoids in high (1.8 mM)‐Ca 2+ medium, but decreased markedly in low (0.09 mM)‐Ca 2+ medium. Interferon‐α‐2a at 1000 IU/ml had an additive growth‐inhibitory effect in the low‐ and in the high‐Ca 2+ medium. No consistent decrease in HPV E6‐E7 mRNA levels could be associated either with retinoid or with interferon effect in either cell line. The expression of TGFβ1 and TGFβ2 mRNA increased 2‐ to 3‐fold by 10 −6 M 13‐ cis ‐RA treatment in early‐ and in late‐passage cells of both cell lines. TGFβ1 at 0.1 to 1.0 ng/ml also inhibited the proliferation of both cell lines, and was more effective at early passage, but the inhibition was not dependent on calcium concentration. Neutralizing anti‐TGFβ antibodies partially relieved the proliferation inhibition by 13‐ cis ‐RA. The results show that the calcium‐associated regulation of growth by the tested retinoids was seen in normal vaginal cells and in early pre‐neoplastic cells, but was significantly reduced in cells with higher‐grade phenotype, while also suggesting that the loss of responsiveness to retinoids and TGFβ may play a role in the progression of squamous intra‐epithelial neoplasia. Int. J. Cancer 78:338–345, 1998.© 1998 Wiley‐Liss, Inc.