Toxicologic Pathology

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here for more information

Click here for more information

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yafan Li,
Right arrow Articles by Oberley, T. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yafan Li,
Right arrow Articles by Oberley, T. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Toxicologic Pathology, Vol. 35, No. 7, 942-951 (2007)
DOI: 10.1080/01926230701748164
© 2007 Society of Toxicologic Pathology

Differential Tumor Biology Effects of Double-Initiation in a Mouse Skin Chemical Carcinogenesis Model Comparing Wild Type versus Protein Kinase Cepsilon Overexpression Mice

Yafan Li

Program in Toxicology & Pharmacology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM

Deric L. Wheeler

Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison

Honnavara N. Ananthaswamy

Department of Immunology, The University of Texas M.D. Anderson Cancer Center

Ajit K. Verma

Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison

Terry D. Oberley

Pathology and Laboratory Medicine Service, VA Hospital, Madison, WI, USA, Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, toberley{at}wisc.edu

Our previous studies showed that protein kinase Cepsilon (PKC{varepsilon}) verexpression in mouse skin resulted in metastatic squamous cell carcinoma (SCC) elicited by single 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion in the absence of preceding papilloma formation as is typically observed in wild type mice. The present study demonstrates that double-DMBA initiation modulates tumor incidence, multiplicity, and latency period in both wild type and PKC{varepsilon} overexpression transgenic (PKC{varepsilon}-Tg) mice. After 17 weeks (wks) of tumor promotion, a reduction in papilloma multiplicity was observed in double- versus single-DMBA initiated wild type mice. Papilloma multiplicity was inversely correlated with cell death indices of interfollicular keratinocytes, indicating decreased papilloma formation was caused by increased cell death and suggesting the origin of papillomas is in interfollicular epidermis. Double-initiated PKC{varepsilon}-Tg mice had accelerated carcinoma formation and cancer incidence in comparison to single-initiated PKC{varepsilon} -Tg mice. Morphologic analysis of mouse skin following double initiation and tumor promotion showed a similar if not identical series of events to those previously observed following single initiation and tumor promotion: putative preneoplastic cells were observed arising from hyperplastic hair follicles (HFs) with subsequent cancer cell infiltration into the dermis. Single-initiated PKC{varepsilon}-Tg mice exhibited increased mitosis in epidermal cells of HFs during tumor promotion.

Key Words: protein kinase Cepsilon • cell death • papilloma • squamous cell carcinoma.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?