HTLV-I pX transgenic rats: development of cytokine-producing mammary carcinomas and establishment of the pX mammary carcinoma cell lines.
In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the HTLV-I pX gene under control of the mouse H-2Kd promoter, mammary carcinomas developed predominantly in females starting at about 5 months of age. The incidence of the tumor reached about 40% when the rats were 12 months old. Histology of the tumor was undifferentiated carcinoma with massive infiltration of granulocytes into the tumor tissue. Systemic granulocytosis and hepato-splenomegaly due to extramedullary granulocytopoiesis were seen in pX rats and nude mice bearing pX mammary tumor. mRNAs of both pX and host genes, Gro and MIP-2, which are granulocyte chemoattractants of the IL-8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene, related with mammary carcinomas, were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats. pX mammary carcinoma cell lines, which have similar characteristics to the primary tumor, were established and the cells underwent apoptosis under the serum deprived conditions. The pX rats and the pX mammary carcinomas appear to be suitable models for analyses of HTLV-I pX oncogenesis and immune pathogenesis in vivo and in vitro.
Shikishima
H
H
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Ikeda
H
H
Yamada
S
S
Yamazaki
H
H
Kikuchi
K
K
Wakisaka
A
A
Kasai
N
N
Shimotono
K
K
Yoshiki
T
T
D000818:Animals; D030801:Animals, Genetically Modified; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006098:Granulocytes / Q000473:pathology; D006183:H-2 Antigens / Q000235:genetics; D006410:Hematopoiesis; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D054334:Viral Regulatory and Accessory Proteins
D016207:Cytokines; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D054334:Viral Regulatory and Accessory Proteins; C072343:pX protein, Human T-lymphotropic virus 1