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- Title
5a-dihydrotestosterone (DHT) inhibits Tumor Necrosis Factor - alpha (TNF-a) induced Janus Kinase-1 (JNK-1) activation and apoptosis in breast cancer in p21 dependent manner.
- Authors
Saini, Karan Singh; Turkar, Vijay; Konwar, Rituraj
- Abstract
Beside established primary reproductive functions, the male hormone androgen act as a growth and survival factor for most of its target tissues. Though male androgenic hormones are widely studied, still some aspects of underlying mechanisms are not completely clear. In addition to their influence on female reproductive hormones which are considered to be crucial factor in breast carcinogenesis, several reports shows that male androgenic hormones may have direct influences on breast cancer tissues. Here, we have used dihydrosterone as model of male androgen to understand its impact on some major molecular circuitry and their by in the process of breast carcinogenesis. We observed that DHT convincingly inhibits tumor necrosis factor-alpha (TNF-α) induced Janus Kinase-1 (JNK-1) activation and apoptosis in breast cancer cells, MCF-7 in p21 dependent manner. Inhibition by androgen requires the transcription activity of androgen receptor (AR) and de novo protein synthesis. AndrogenAR induces expression of p21 that in turn inhibits tumor necrosis factor-a induced JNK activation and apoptosis. Our results reveal a novel cross-talk between AR and JNK in breast cancer (MCF-7) cells, thereby providing a molecular mechanism underlying the survival function of androgen on its target tissues or organ.
- Subjects
TUMOR necrosis factors; JANUS kinases; BREAST cancer
- Publication
Journal of Recent Advances in Applied Sciences, 2022, p1
- ISSN
0970-1990
- Publication type
Article