The effect of parity, tumor latency and transplantation on the activation of int loci in MMTV-induced, transplanted C3H mammary pre-neoplasias and their tumors.
Mouse mammary tumor virus (MMTV) infection of mammary glands results in proviral insertion into host DNA and activation of cellular genes. Clonal expansion of cells bearing insertional mutations results in hyperplastic alveolar nodules (HAN) and tumors. HAN, transplanted into epithelium-cleared mammary fat pads, form hyperplastic alveolar outgrowths (HOGs). Previous work indicates the commonly MMTV-activated genes wnt-1 and int-2 are rarely affected in HOGs and HOG-derived tumors. To determine the basis of the dichotomy between the frequency of wnt/int gene activation in HOG-derived tumors and tumors from breeders of the identical inbred mouse strain, we compared the activation of wnt-1, int-2 and int-3 in tumors from virgin and breeding C3H mice, in consecutive primary tumors arising in individual C3H breeders and in C3H HOGs at early passages. Activation of wnt-1 or int-2 was rare in HOG-derived tumors (6% and 0%) compared with primary tumors in breeders (52% and 14%). int-3 was never found to be activated. wnt-1 was activated in the same percentage of primary tumors from virgins as from breeders. int-2 was activated only in tumors from breeders. wnt-1 activation also did not correlate with shorter tumor latency in multiple tumors from individual breeders. wnt-1 RNA was not detected in HOGs at early transplant generations, however, low levels of wnt-1 RNA were variably found in the epithelium of virgin mammary glands. We cannot explain why C3H HOGs and their derivative tumors develop without wnt-1 expression when the majority of C3H primary mammary tumors possess an MMTV-activated wnt-1 gene.
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
M S
MS
Schwartz
G H
GH
Smith
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D
Medina
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010298:Parity; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics; D015533:Transcriptional Activation
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm