Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression

Mariana C. Stern, Irma B. Gimenez-Conti, Irina Budunova, Lezlee Coghlan, Susan M. Fischer, John DiGiovanni, Thomas J Slaga, Claudio J. Conti

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The SENCAR stock of mice has proved to be a useful model in dissecting out the multistage nature as well as the critical mechanisms involved in skin tumorigenesis. This outbred stock was selectively bred to be susceptible to initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice more suitable for genetic analyses of tumor susceptibility and tissue transplantation studies, several inbred lines of mice were derived from the SENCAR stock. One of these lines, the SSIN mice, has a higher susceptibility to tumor promotion compared to the SENCAR stock but is very resistant to tumor progression. On the other hand, the SENCAR B/Pt mice, derived also from the outbred stock, not only have a tumor promotion susceptibility almost identical to the SSIN mice, but they also have a high susceptibility to tumor progression. In order to understand the nature of the phenotypic differences between these two inbred lines we have characterized them using several parameters and markers that are associated with the progression of papillomas to squamous cell carcinoma (SCC). In this sense we analysed the tumor multiplicity and SCC incidence, and the expression of markers of progression and cell cycle related proteins in papillomas derived from both strains. Our results showed that while both strains have a similar papilloma multiplicity and incidence the SENCAR B/Pt mice have 67% incidence of SCC, compared to O% in the SSIN. SENCAR B/Pt papillomas at 30 weeks of promotion have a higher and aberrant expression of K13, and loss of connexin 26. TGF-β1 was found to be over-expressed in the suprabasal and superficial cells in the SENCAR B/Pt papillomas, while it was only expressed in the superficial cell layer in those derived from SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferative compartment with overexpression of cyclin D1 and PCNA as seen by immunohistochemistry and Western blot.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalCarcinogenesis
Volume19
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Fingerprint

Inbred Strains Mice
Papilloma
Skin
Squamous Cell Carcinoma
Neoplasms
Incidence
Inbred SENCAR Mouse
Tissue Transplantation
9,10-Dimethyl-1,2-benzanthracene
Cell Cycle Proteins
Cyclin D1
Proliferating Cell Nuclear Antigen
Tetradecanoylphorbol Acetate
Carcinogenesis
Western Blotting
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research

Cite this

Stern, M. C., Gimenez-Conti, I. B., Budunova, I., Coghlan, L., Fischer, S. M., DiGiovanni, J., ... Conti, C. J. (1998). Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression. Carcinogenesis, 19(1), 125-132. https://doi.org/10.1093/carcin/19.1.125

Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression. / Stern, Mariana C.; Gimenez-Conti, Irma B.; Budunova, Irina; Coghlan, Lezlee; Fischer, Susan M.; DiGiovanni, John; Slaga, Thomas J; Conti, Claudio J.

In: Carcinogenesis, Vol. 19, No. 1, 01.1998, p. 125-132.

Research output: Contribution to journalArticle

Stern, MC, Gimenez-Conti, IB, Budunova, I, Coghlan, L, Fischer, SM, DiGiovanni, J, Slaga, TJ & Conti, CJ 1998, 'Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression', Carcinogenesis, vol. 19, no. 1, pp. 125-132. https://doi.org/10.1093/carcin/19.1.125
Stern, Mariana C. ; Gimenez-Conti, Irma B. ; Budunova, Irina ; Coghlan, Lezlee ; Fischer, Susan M. ; DiGiovanni, John ; Slaga, Thomas J ; Conti, Claudio J. / Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression. In: Carcinogenesis. 1998 ; Vol. 19, No. 1. pp. 125-132.
@article{123de1d4bf2f4a2f9404941992588b94,
title = "Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression",
abstract = "The SENCAR stock of mice has proved to be a useful model in dissecting out the multistage nature as well as the critical mechanisms involved in skin tumorigenesis. This outbred stock was selectively bred to be susceptible to initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice more suitable for genetic analyses of tumor susceptibility and tissue transplantation studies, several inbred lines of mice were derived from the SENCAR stock. One of these lines, the SSIN mice, has a higher susceptibility to tumor promotion compared to the SENCAR stock but is very resistant to tumor progression. On the other hand, the SENCAR B/Pt mice, derived also from the outbred stock, not only have a tumor promotion susceptibility almost identical to the SSIN mice, but they also have a high susceptibility to tumor progression. In order to understand the nature of the phenotypic differences between these two inbred lines we have characterized them using several parameters and markers that are associated with the progression of papillomas to squamous cell carcinoma (SCC). In this sense we analysed the tumor multiplicity and SCC incidence, and the expression of markers of progression and cell cycle related proteins in papillomas derived from both strains. Our results showed that while both strains have a similar papilloma multiplicity and incidence the SENCAR B/Pt mice have 67{\%} incidence of SCC, compared to O{\%} in the SSIN. SENCAR B/Pt papillomas at 30 weeks of promotion have a higher and aberrant expression of K13, and loss of connexin 26. TGF-β1 was found to be over-expressed in the suprabasal and superficial cells in the SENCAR B/Pt papillomas, while it was only expressed in the superficial cell layer in those derived from SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferative compartment with overexpression of cyclin D1 and PCNA as seen by immunohistochemistry and Western blot.",
author = "Stern, {Mariana C.} and Gimenez-Conti, {Irma B.} and Irina Budunova and Lezlee Coghlan and Fischer, {Susan M.} and John DiGiovanni and Slaga, {Thomas J} and Conti, {Claudio J.}",
year = "1998",
month = "1",
doi = "10.1093/carcin/19.1.125",
language = "English (US)",
volume = "19",
pages = "125--132",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression

AU - Stern, Mariana C.

AU - Gimenez-Conti, Irma B.

AU - Budunova, Irina

AU - Coghlan, Lezlee

AU - Fischer, Susan M.

AU - DiGiovanni, John

AU - Slaga, Thomas J

AU - Conti, Claudio J.

PY - 1998/1

Y1 - 1998/1

N2 - The SENCAR stock of mice has proved to be a useful model in dissecting out the multistage nature as well as the critical mechanisms involved in skin tumorigenesis. This outbred stock was selectively bred to be susceptible to initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice more suitable for genetic analyses of tumor susceptibility and tissue transplantation studies, several inbred lines of mice were derived from the SENCAR stock. One of these lines, the SSIN mice, has a higher susceptibility to tumor promotion compared to the SENCAR stock but is very resistant to tumor progression. On the other hand, the SENCAR B/Pt mice, derived also from the outbred stock, not only have a tumor promotion susceptibility almost identical to the SSIN mice, but they also have a high susceptibility to tumor progression. In order to understand the nature of the phenotypic differences between these two inbred lines we have characterized them using several parameters and markers that are associated with the progression of papillomas to squamous cell carcinoma (SCC). In this sense we analysed the tumor multiplicity and SCC incidence, and the expression of markers of progression and cell cycle related proteins in papillomas derived from both strains. Our results showed that while both strains have a similar papilloma multiplicity and incidence the SENCAR B/Pt mice have 67% incidence of SCC, compared to O% in the SSIN. SENCAR B/Pt papillomas at 30 weeks of promotion have a higher and aberrant expression of K13, and loss of connexin 26. TGF-β1 was found to be over-expressed in the suprabasal and superficial cells in the SENCAR B/Pt papillomas, while it was only expressed in the superficial cell layer in those derived from SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferative compartment with overexpression of cyclin D1 and PCNA as seen by immunohistochemistry and Western blot.

AB - The SENCAR stock of mice has proved to be a useful model in dissecting out the multistage nature as well as the critical mechanisms involved in skin tumorigenesis. This outbred stock was selectively bred to be susceptible to initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice more suitable for genetic analyses of tumor susceptibility and tissue transplantation studies, several inbred lines of mice were derived from the SENCAR stock. One of these lines, the SSIN mice, has a higher susceptibility to tumor promotion compared to the SENCAR stock but is very resistant to tumor progression. On the other hand, the SENCAR B/Pt mice, derived also from the outbred stock, not only have a tumor promotion susceptibility almost identical to the SSIN mice, but they also have a high susceptibility to tumor progression. In order to understand the nature of the phenotypic differences between these two inbred lines we have characterized them using several parameters and markers that are associated with the progression of papillomas to squamous cell carcinoma (SCC). In this sense we analysed the tumor multiplicity and SCC incidence, and the expression of markers of progression and cell cycle related proteins in papillomas derived from both strains. Our results showed that while both strains have a similar papilloma multiplicity and incidence the SENCAR B/Pt mice have 67% incidence of SCC, compared to O% in the SSIN. SENCAR B/Pt papillomas at 30 weeks of promotion have a higher and aberrant expression of K13, and loss of connexin 26. TGF-β1 was found to be over-expressed in the suprabasal and superficial cells in the SENCAR B/Pt papillomas, while it was only expressed in the superficial cell layer in those derived from SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferative compartment with overexpression of cyclin D1 and PCNA as seen by immunohistochemistry and Western blot.

UR - http://www.scopus.com/inward/record.url?scp=0031820169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031820169&partnerID=8YFLogxK

U2 - 10.1093/carcin/19.1.125

DO - 10.1093/carcin/19.1.125

M3 - Article

C2 - 9472703

AN - SCOPUS:0031820169

VL - 19

SP - 125

EP - 132

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 1

ER -