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Generation of a tissue‐specific transgenic model for K8 phosphomutants: A tool to investigate the role of K8 phosphorylation during skin carcinogenesis in vivo
Author(s) -
Tiwari Richa,
Ganguli Nirmalya,
Alam Hunain,
Sahu Indrajit,
Vadivel Chella Krishna,
Sinha Shruti,
Patel Shweta,
Jamghare Sayli Nitin,
Bane Sanjay,
Thorat Rahul,
Majumdar Subeer S.,
Vaidya Milind M.
Publication year - 2021
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11611
Subject(s) - keratin , keratin 8 , carcinogenesis , keratin 5 , phosphorylation , keratin 14 , biology , neoplastic transformation , cancer research , transgene , microbiology and biotechnology , genetically modified mouse , cancer , biochemistry , genetics , gene
Keratin 8/18, the predominant keratin pair of simple epithelia, is known to be aberrantly expressed in several squamous cell carcinomas (SCCs), where its expression is often correlated with increased invasion, neoplastic progression, and poor prognosis. The majority of keratin 8/18 structural and regulatory functions are governed by posttranslational modifications, particularly phosphorylation. Apart from filament reorganization, cellular processes including cell cycle, cell growth, cellular stress, and apoptosis are known to be orchestrated by K8 phosphorylation at specific residues in the head and tail domains. Even though deregulation of K8 phosphorylation at two significant sites (Serine 73 /Serine 431 ) has been implicated in neoplastic progression of SCCs by various in vitro studies, including ours, it is reported to be highly context‐dependent. Therefore, to delineate the precise role of Kereatin 8 phosphorylation in cancer initiation and progression, we have developed the tissue‐specific transgenic mouse model expressing Keratin 8 wild type and phosphodead mutants under Keratin 14 promoter. Subjecting these mice to 7,12‐dimethylbenz( a )anthracene/12‐ O ‐tetradecanoylphorbol‐13‐acetate‐mediated skin carcinogenesis revealed that Keratin 8 phosphorylation may lead to an early onset of tumors compared to Keratin 8 wild‐type expressing mice. Conclusively, the transgenic mouse model developed in the present study ascertained a positive impact of Keratin 8 phosphorylation on the neoplastic transformation of skin‐squamous cells.