Reference SummaryLeder A, Proc Natl Acad Sci U S A 1990 Dec;87(23):9178-82

Title

 v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid.

Authors

 Leder A; Kuo A; Cardiff RD; Sinn E; Leder P

Journal

 Proc Natl Acad Sci U S A

Volume

 87

Issue

 23

Year

 1990

Pages

 9178-82

Abstract

 Experimental carcinogenesis has led to a concept that defines two discrete stages in the development of skin tumors: (i) initiation, which is accomplished by using a mutagen that presumably activates a protooncogene, and (ii) promotion, which is a reversible process brought about most commonly by repeated application of phorbol esters. We have created a transgenic mouse strain that carries the activated v-Ha-ras oncogene fused to the promoter of the mouse embryonic alpha-like, zeta-globin gene. Unexpectedly, these animals developed papillomas at areas of epidermal abrasion and, because abrasion can also serve as a tumor-promoting event in mutagen-treated mouse skin, we tested these mice for their ability to respond to phorbol ester application. Within 6 weeks virtually all treated carrier mice had developed multiple papillomas, some of which went on to develop squamous cell carcinomas and, more frequently, underlying sarcomas. We conclude that the oncogene preinitiates carrier mice, replacing the initiation/mutagenesis step and immediately sensitizing them to the action of tumor promoters. In addition, treatment of the mice with retinoic acid dramatically delays, reduces, and often completely inhibits the appearance of promoter-induced papillomas. This strain has use in screening tumor promoters and for assessing antitumor and antiproliferative agents.

Links

 J:55016 – MGI References
2251261 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Expression of the "TG.AC" transgene was reported to not be detected in the pancreas, brain, colon, small intestine, striated muscle, mammary glands, testis, liver, kidney, salivary glands, skin, thymus, and spleen of these mice.
The "TG.AC" transgene was reported to be expressed in the placenta, blood, liver, and keratinocytes, and slightly expressed in the bone marrow of these mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N Mesodermal cell/mesoblast sarcoma - spindle cell Skin

0
FVB/N Mesodermal cell/mesoblast sarcoma - spindle cell
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

0
FVB/N Mesodermal cell/mesoblast sarcoma - spindle cell
  • retinoic acid (RA)
 Skin

0
FVB/N Mesodermal cell/mesoblast sarcoma - spindle cell
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
  • retinoic acid (RA)
 Skin

0
FVB/N Mesodermal cell/mesoblast sarcoma - spindle cell
  • wounding
 Skin

0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Mesodermal cell/mesoblast sarcoma - spindle cell Skin

0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Mesodermal cell/mesoblast sarcoma - spindle cell
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Mesodermal cell/mesoblast sarcoma - spindle cell
  • retinoic acid (RA)
 Skin

0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Mesodermal cell/mesoblast sarcoma - spindle cell
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
  • retinoic acid (RA)
 Skin

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Mesodermal cell/mesoblast sarcoma - spindle cell
  • wounding
 Skin

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin hyperplasia
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

observed
FVB/N Skin hyperplasia
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin keratoacanthoma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • wounding
 Skin

observed - 100
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma Skin

0
FVB/N Skin papilloma Skin

0
FVB/N Skin papilloma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

0
FVB/N Skin papilloma
  • retinoic acid (RA)
 Skin

0
FVB/N Skin papilloma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
  • retinoic acid (RA)
 Skin

0
FVB/N Skin papilloma
  • wounding
 Skin

0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

97
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • retinoic acid (RA)
 Skin

0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
  • retinoic acid (RA)
 Skin

25 - 42
FVB/N Skin squamous cell carcinoma Skin

0
FVB/N Skin squamous cell carcinoma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

0
FVB/N Skin squamous cell carcinoma
  • retinoic acid (RA)
 Skin

0
FVB/N Skin squamous cell carcinoma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
  • retinoic acid (RA)
 Skin

0
FVB/N Skin squamous cell carcinoma
  • wounding
 Skin

0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin squamous cell carcinoma Skin

0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin squamous cell carcinoma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
 Skin

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin squamous cell carcinoma
  • retinoic acid (RA)
 Skin

0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin squamous cell carcinoma
  • phorbol 12-myristate 13-acetate (phorbol ester) (PMA)
  • retinoic acid (RA)
 Skin

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin squamous cell carcinoma
  • wounding
 Skin

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Spleen hyperplasia Spleen

observed