Keratinocyte p38δ loss inhibits Ras-induced tumor formation, while systemic p38δ loss enhances skin inflammation in the early phase of chemical carcinogenesis in mouse skin

Molecular Carcinogenesis
Alexi KissTatiana Efimova

Abstract

p38δ expression and/or activity are increased in human cutaneous malignancies, including invasive squamous cell carcinoma (SCC) and head and neck SCC, but the role of p38δ in cutaneous carcinogenesis has not been well-defined. We have reported that mice with germline loss of p38δ exhibited a reduced susceptibility to skin tumor development compared with wild-type mice in the two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical skin carcinogenesis model. Here, we report that p38δ gene ablation inhibited the growth of tumors generated from v-ras(Ha) -transformed keratinocytes in skin orthografts to nude mice, indicating that keratinocyte-intrinsic p38δ is required for Ras-induced tumorigenesis. Gene expression profiling of v-ras(Ha) -transformed p38δ-null keratinocytes revealed transcriptional changes associated with cellular responses linked to tumor suppression, such as reduced proliferation and increased differentiation, cell adhesion, and cell communications. Notably, a short-term DMBA/TPA challenge, modeling the initial stages of chemical skin carcinogenesis treatment, elicited an enhanced inflammation in p38δ-null skin compared with skin of wild-type mice, as assessed by measur...Continue Reading

References

Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·A W Lin, S W Lowe
Jan 10, 2003·The Journal of Investigative Dermatology. Symposium Proceedings·Andrzej DlugoszStuart H Yuspa
Jan 18, 2005·Seminars in Cancer Biology·Adam B Glick, Stuart H Yuspa
Apr 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Saveria PastoreGiampiero Girolomoni
Jan 7, 2006·Nature Reviews. Cancer·Karin E de VisserLisa M Coussens
Jan 6, 2007·The Journal of Investigative Dermatology·Eva M SchindlerTatiana Efimova
Feb 17, 2007·Current Opinion in Cell Biology·Claire R Weston, Roger J Davis
May 15, 2007·Oncogene·M RamanM H Cobb
May 22, 2009·Cancer Research·Eva M SchindlerTatiana Efimova
Jun 24, 2009·The Journal of Cell Biology·Spiro GetsiosKathleen J Green
Jul 25, 2009·Nature Reviews. Cancer·Erwin F Wagner, Angel R Nebreda
Jun 10, 2010·PLoS Pathogens·Young Jun KangJiahuai Han
Jul 16, 2010·The Biochemical Journal·Ana Cuadrado, Angel R Nebreda
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
May 12, 2011·Carcinogenesis·M Isabel Cerezo-GuisadoAna Cuenda
Sep 24, 2011·American Journal of Physiology. Cell Physiology·V'yacheslav Lehen'kyiNatalia Prevarskaya
Jan 3, 2012·Seminars in Cancer Biology·Frances R Balkwill, Alberto Mantovani
Mar 1, 2012·Nature Reviews. Cancer·Esther N ArwertFiona M Watt
Mar 24, 2012·Cancer Cell·Douglas Hanahan, Lisa M Coussens
May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Patcharee RitprajakJin Mo Park
Jul 10, 2012·The Journal of Clinical Investigation·Juan Guinea-ViniegraErwin F Wagner
Nov 16, 2012·The Journal of Investigative Dermatology·Congxing LinTatiana Efimova
Jul 24, 2013·Molecular and Cellular Biology·Jinny KwongPeiqing Sun

❮ Previous
Next ❯

Citations

Apr 3, 2019·International Journal of Molecular Sciences·Alexi KissTatiana Efimova
May 1, 2021·Biomolecules·Massimo PancioneAlmudena Porras
Jul 3, 2021·International Journal of Molecular Sciences·Josefa P AlamedaMaría Llanos Casanova

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.