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D Medina

Publications and source records attributed to D Medina.

At least 91 records · Page 5Linked to original sources
PubMed1995

Tyrosine phosphorylation in mouse mammary hyperplasias.

Tyrosine phosphorylation status was investigated during mouse mammary tumor development using non-tumorigenic and tumorigenic hyperplastic outgrowth lines. These outgrowth lines were compared with normal mammary glands from pregnant mice and with their corresponding tumors. The levels of total tyrosine phosphorylation in proteins of hyperplastic and neoplastic tissues were 4.7- and 3.4-fold higher than in the normal gland respectively. These results indicate that increases in tyrosine phosphorylation occur in the earliest stages of neoplastic development and are not restricted to neoplastic cells per se. These results led to the identification of the specific proteins showing high levels of tyrosine phosphorylation. Of the eight molecular weight bands of proteins exhibiting detectable levels of tyrosine phosphorylation, the only proteins exhibiting consistently different degrees of phosphorylation between hyperplasias and tumors were of approximately 34 kDa. In a series of six different hyperplasias with tumorigenic potentials ranging from 0 to 93%, the extent of tyrosine phosphorylation of 34 kDa proteins correlated inversely with tumorigenic potential. The levels of p34cdc2 and p33cdk2 proteins were examined, using antibodies specific for the cdc2 and cdk2 proteins. The amounts of p34cdc2 and p33cdk2 proteins were low in non-tumorigenic (TM3 and TM2L) compared to tumorigenic hyperplasias and correlated inversely with tyrosine phosphorylation of 34 kDa proteins during tumor development. Thus in the non-tumorigenic hyperplasias (TM2L and TM3) the majority of p34cdc2 was phosphorylated on tyrosine, in contrast to the p34cdc2 in tumorigenic (TM2H) hyperplasias and tumors. Two-dimensional PAGE analysis of mammary tumor samples with antibodies specific to cdc2, cdk2 and phosphorylated tyrosine revealed one p34cdc2 form, two p33cdk2 isoforms and two phosphotyrosine isoforms of about 33-34 kDa. The results suggest that the high levels of tyrosine phosphorylation in cdc2 and cdk2 reflect the low tumorigenic potential of a subset of mammary preneoplastic hyperplasias. This interpretation is in accord with current concepts on the role of tyrosine phosphorylation in the regulation of the cyclin-dependent kinases.

Animals↗
PubMed1995

Incidence and risk factors for early small bowel obstruction after celiotomy for penetrating abdominal trauma.

The reported overall incidence of postoperative Small Bowel Obstruction (SBO) is 0.69 per cent. This study examined the incidence and risk factors for early postoperative SBO for penetrating abdominal trauma (PAT), with early SBO defined as SBO within 6 months of operation. This was a prospective cohort study of patients admitted to a Level 1 Trauma Center from 5/91 to 12/93 who required celiotomy for PAT. Patients were followed at least 6 months for readmission for SBO to be considered evaluable. Of 341 patients undergoing celiotomy for PAT and surviving to discharge, 298 (87.4%) were evaluable. The overall incidence of early SBO was 7.4 per cent and varied between 2.3 per cent (nontherapeutic celiotomy) and 10.8 per cent (small/large bowel injury). All patients with celiotomy for PAT are at increased risk for early SBO compared with elective surgery patients. Those with small/large bowel penetration or gunshot wounds are at the highest risk. Previous abdominal surgery is not a risk factor for early SBO in PAT patients. Surgeons and Managed Care case managers should devote special attention to close follow-up in PAT patients, particularly those with the risk factors identified in this study.

Abdominal Injuries↗
PubMed1994

Infrequent p53 mutations in 7,12-dimethylbenz[a]anthracene-induced mammary tumors in BALB/c and p53 hemizygous mice.

We conducted experiments to determine if p53 alterations, which are frequent in human breast cancers, were also common in murine mammary tumors. In 13 mammary tumors from 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/c mice were immunohistochemically analyzed for overexpression of p53; p53 protein was not detectable. Three of the tumors were established as cell lines in vitro. p53 protein was rarely detected at passage 4 in these lines but was overexpressed by passage 8 in two of them. The p53 nucleotide sequence was shown to be wild type in one primary mammary tumor and in the two p53-overexpressing cell lines. One cell line that overexpressed p53 in vitro was implanted into BALB/c mice. The resulting tumors retained the wild-type p53 nucleotide sequence but no longer expressed detectable levels of p53 protein, suggesting that the overexpression of wild-type p53 was related to in vitro culture conditions. The effect of DMBA on mammary-tumor development was also tested in mice rendered hemizygous for p53. These mice and wild-type littermate controls had no differences in susceptibility to induction of mammary tumors by oral administration of DMBA. Furthermore, Southern blot hybridization detected no gross alterations in the wild-type p53 allele in mammary tumors from the p53-deficient mice. Point mutation of the wild-type p53 allele was also infrequent in the DMBA-induced mammary tumors from hemizygous p53 mice; it occurred in only one of seven tumors. Thus, the p53 gene is apparently not a primary target for genetic alterations in DMBA-induced mammary tumors. Next, we examined mammary tumors derived from D1 and D2 transplantable hyperplastic alveolar nodule (HAN) outgrowths, which rapidly form tumors containing Ha-ras mutations after DMBA treatment. As ras and p53 mutants can cooperate in transformation, we examined whether D1 and D2 HAN outgrowths have p53 mutations. Unlike in the DMBA-induced primary mammary tumors, nuclear p53 accumulation was observed frequently (10 of 14) in tumors that arose from D1 and D2 HAN outgrowths. Direct sequencing of the entire coding region of the p53 cDNA from six D1 and D2 tumors confirmed that the sequence was wild type. Although wild-type p53 was retained in both DMBA-induced mammary tumors and mammary tumors derived from D1 and D2 preneoplastic outgrowths, wild-type p53 overexpression was detected only in D1 and D2 tumors. Therefore, D1 and D2 tumors appear to arise by a pathway in which p53 expression is altered, whereas DMBA induction affects a different pathway that does not require such alteration.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

[Biophysical profile in twin pregnancy: prospective study].

The biophysical profile is an excellent test for assessment of the fetoplacental unit, for analyze is value in twin gestation, we study prospectively 81 multiple gestations. The fetuses were examined weekly antepartum. We use the modified profile of Manning which include only the sonographic criteria: the figures for predict stillborn were: sensitivity of 66.7%, specificity of 98.8%, positive predictive value of 50% and negative predictive value of 99.4% and predict between distressed and healthy fetus of a pair; 94.6% of fetus perform good biophysical profile score twenty minutes. We conclude that the fetal biophysical profile is the elective tool in the assessment of twin gestations.

Adolescent↗
PubMed1994

Preferential overexpression of a 172Arg-->Leu mutant p53 in the mammary gland of transgenic mice results in altered lobuloalveolar development.

Regulatory sequences derived from the rat whey acidic protein gene have been used to preferentially overexpress a murine 172Arg-->Leu mutant p53 in the mammary gland of transgenic mice. Several different lines of mice expressing the 172Arg-->Leu mutant p53 displayed an impaired ability to lactate, and the mice expressing the highest levels of mutant p53 were unable to nurse their young. This failure was related to the inhibition of normal lobuloalveolar development that occurred during late pregnancy and a marked decrease in milk protein gene expression at early lactation. Interestingly, immunohistochemical analysis revealed that the mutant p53 was localized predominantly in the cytoplasm of alveolar cells. Ductal development was not overtly impaired in these mice. Expression of the 172Arg-->Leu mutant p53 resulted in radiation-induced apoptosis, and transactivation or repression of the expression of a number of genes, including mdm-2 and proliferating cell nuclear antigen, known properties of wild-type p53. The availability of lines of mice preferentially expressing specific p53 mutants in the mammary gland should facilitate evaluation of the roles of other factors, such as hormones, oncogenes and chemical carcinogens, in the etiology of breast cancer.

Animals↗
PubMed1993

Mutations in p53 are frequent in the preneoplastic stage of mouse mammary tumor development.

Preneoplastic lesions in the mammary gland represent a population of cells at increased risk of progression to tumors. Because p53 is the most commonly mutated gene in human breast cancer, we sought to determine whether mutations in p53 were present in preneoplastic lesions or were acquired during progression to overt tumors. In the mouse mammary gland, hyperplastic alveolar nodules (HAN) are the most common preneoplastic lesion. Analysis of the TM series of transplantable murine HAN outgrowths and tumors allowed the status of p53 to be determined at distinct stages of mammary tumorigenesis. Alterations in the p53 gene or in the pattern of p53 protein expression were observed in all five HAN outgrowth lines examined. Altered expression of p53 protein was detected in 3 of 5 TM HAN outgrowth lines as determined by immunohistochemistry. Overexpression of nuclear p53 was detected in only a fraction of the cells (10-50%) in TM3 and TM4 HAN outgrowths, whereas in tumors that arose from TM4 HAN outgrowths, the proportion of cells overexpressing p53 protein approached approximately 100%. Despite overexpression of p53 in TM3 HAN outgrowths, no tumors have developed in this line. The TM9 outgrowth line exhibited a different pattern of p53 expression by immunohistochemistry: p53 protein was overexpressed in the cytoplasm of virtually all cells in the HAN outgrowths but was localized to the nuclei of TM9 tumor cells. Direct sequencing of p53 transcripts from tumors and cell lines revealed various genetic changes: point mutations in exons 4 and 5 (TM2H, nonsense; TM4, missense); a deletion in exon 5 (TM4); and an insertion in exon 7 (TM3). Although p53 protein was overexpressed in TM9 tumors, it was shown to be wild-type both by immunoprecipitation and direct sequencing of the entire coding region of the cDNA. TM4 cells were homogeneous with respect to mutant p53 genotype and uniformly expressed p53 by immunohistochemical staining in vitro, but transplantation of TM4 cells to fat pads of BALB/c hosts resulted in HAN outgrowths in situ in which < 50% of the cells expressed the mutant p53 at detectable levels. In summary, mutation of the p53 gene and overexpression of p53 protein can occur in preneoplastic mammary epithelial cells, and those mutations are maintained in tumors that arise from the HAN. Conversely, expression of mutant p53 was decreased when cells were grown in situ, implicating the presence of cellular factors that can suppress p53 expression in vivo. These observations demonstrate that the p53 pathway may be a common target for mutation in murine mammary tumorigenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

p53 mutations selected in vivo when mouse mammary epithelial cells form hyperplastic outgrowths are not necessary for establishment of mammary cell lines in vitro.

Breast cancer is a consequence of multiple alterations occurring over a long period of time. Genetic changes in early stages of tumorigenesis have not been defined. A recently developed murine system permits the study of mammary preneoplastic cells in vivo and in vitro (F. S. Kittrell et al., Cancer Res., 52: 1924-1932, 1992). To assess the potential role of p53 mutations in early stages of breast cancer, the status of p53 was determined in a series of mouse mammary epithelial cell lines which give rise to preneoplastic outgrowths (hyperplastic alveolar nodules) when transplanted into cleared mammary fat pads of syngeneic mice. Protein stability and conformation were analyzed using immunoprecipitations and immunochemical assays; p53 transcripts were sequenced using a polymerase chain reaction approach. The parental cell lines (FSK lines) showed no evidence of p53 alterations at either the protein or the nucleic acid level, indicating that p53 mutations are not essential for the establishment of mammary epithelial cell lines in vitro. In contrast, cell lines (TM lines) derived from hyperplastic alveolar nodule outgrowths induced by FSK cells expressed only mutant p53 genes. The mutation in one outgrowth cell line (TM-2H) resulted in the loss of p53 protein synthesis, whereas two other outgrowth lines (TM-3, TM-4) overexpressed mutant p53 protein. Mutation of p53 appears to correlate with preneoplastic growth in vivo. Although it is not clear if the mutations occur before or after transplantation of cells in vivo, there appears to be a pronounced growth advantage in the mammary gland for cells expressing mutant p53.

Animals↗
PubMed1993

Expression of fatty acid-binding proteins in the developing mouse mammary gland.

Proteins of 14,000 daltons (SLP-14) were isolated and partially characterized from mouse mammary glands of different developmental stages. The purified proteins were partially sequenced at the amino acid level. The SLP-14 belong to the family of fatty acid-binding (FABP) proteins. The major SLP-14 expressed was a reflection of the differentiation stage of the mammary gland. Within the regions sequenced for each protein, virgin mouse mammary gland (primarily adipocytes) expressed a protein 100% homologous to adipocyte lipid binding protein whereas pregnant and lactating mouse mammary glands expressed a protein highly homologous to mouse heart fatty acid binding protein. In the lactating gland, the isolated protein was 97% identical to the heart FABP over a 98 amino acid stretch. We could not detect the 14Kd protein identified as mammary gland growth inhibitor (MDGI) which is also a member of the FABP family and highly homologous to heart FABP. A rabbit antiserum to the rat mammary SLP-14 recognized the SLP-14 proteins in mouse and rat mammary gland, skeletal muscle and heart, whereas it failed to recognize the SLP-14 in liver, intestine and other organs. These data indicate that the SLP-14 detected in rodent mammary gland is of the fatty acid-binding protein family. On the basis of amino acid sequence, the major form in the differentiated mouse mammary gland is apparently FABP and not MDGI. MDGI may be a protein in low abundance and/or localized to a specific group of mammary epithelial cells.

Amino Acid Sequence↗
PubMed1993

Morphological and functional properties of TM preneoplastic mammary outgrowths.

The TM series of preneoplastic mammary outgrowth lines was derived from the transplantation of the FSK mammary cell lines into the cleared mammary fat pads of syngeneic female BALB/c mice. The tumor-producing capabilities of the 6 TM outgrowth lines varied from high (TM2, -4, -6) to low (TM9, -10) to nil (TM3). Outgrowth lines 2, 4, and 6 each segregated into sublines of high and low tumor potential. The majority of the outgrowth lines exhibited a moderate to dense alveolar hyperplasia typical of mouse mammary hyperplasias. The exceptions to this picture were lines TM2H and TM10 which exhibited a unique ductular morphology. The ductular morphology was not correlated with tumor potential of the outgrowth lines but was correlated with the expression of K6 and K14 keratins in luminal epithelial cells. In an examination of the growth and hormonal responsiveness properties of the TM outgrowth lines, the TM3 line stands as distinct from the other lines and from any other lines previously characterized in BALB/c mice. The TM3 line grew very slowly and failed to fill the fat pad by 12 months of age. At 12 months of age, the alveolar hyperplasia had regressed so that only bare ducts were present. The TM3 outgrowth was ovarian hormone dependent for growth and alveolar differentiation. TM3 outgrowth represents a minimally deviated mammary hyperplasia which has acquired the immortal phenotype but not the other phenotypic characteristics of mammary preneoplasias. This outgrowth line will be useful for examining the essential molecular changes important for the preneoplastic state, some of which are reported in an accompanying paper (D. Medina et al., Cancer Res., 53: 668-674, 1993).

Animals↗
PubMed1993

Growth factor dependency and gene expression in preneoplastic mouse mammary epithelial cells.

The TM preneoplastic mammary outgrowth lines were established in vivo from mammary epithelial cell lines and have been characterized with respect to their tumorigenic, morphological, and functional properties. The TM outgrowth lines were then established as in vitro cell lines. A comparison of the growth factor dependencies of the TM preneoplastic lines and their progenitor cell lines grown in monolayer cell culture indicated that the TM preneoplastic cell lines exhibited a decreased dependence on epidermal growth factor for growth in vitro. The exception to this result was the TM3 cell line which still exhibited a marked dependence on epidermal growth factor for growth. An examination of several genes for mRNA levels indicated that the expression of c-neu, c-H-ras, c-myc, and retinoblastoma was not elevated in those TM preneoplasias which exhibited a decreased dependence on epidermal growth factor. Additionally, there was no evidence that c-H-ras was activated in the preneoplastic outgrowths or tumors. In contrast, mouse mammary tumor virus long terminal repeat mRNA was increased in preneoplasias and tumors, whereas gelsolin mRNA was decreased in tumors but not in preneoplasias. The down-regulation of gelsolin mRNA is consistent with recent reports in human breast cancers. These results together with those reported in another paper (D. Medina et al., Cancer Res., 53: 663-667, 1993) indicate that the TM3 outgrowth line is a minimally deviated preneoplasia which does not share many of the molecular alterations exhibited in tumorigenic TM preneoplastic outgrowth lines. These data, along with other recent data, are interpreted in a hypothesis which views the three essential characteristics of the mammary preneoplastic state as independent and dissociable genetic alterations. Importantly, each of the three characteristics is independently isolated in one or more of the in vivo outgrowth populations. These outgrowth lines should allow identification of the nature and function of the molecular alterations associated with each stage of mammary preneoplasia.

Animals↗
PubMed1993

Gene expression screening for specific genes associated with mouse mammary tumor development.

The preneoplastic hyperplastic alveolar nodule is a frequent and well-characterized precursor to mammary tumors in the mouse. Although the biological characteristics of the preneoplastic state have been understood for many years, the molecular alterations associated with preneoplasia and tumorigenicity are unknown. We applied the technique of differential display of mRNA to two closely matched cell populations of mammary preneoplasias that differed only in their tumorigenic potential. Two mRNAs were isolated that were overexpressed only in tumorigenic preneoplasias and in tumors and not in normal pregnant mammary gland or in nontumorigenic preneoplasias. Partial nucleotide sequencing indicated that one of the mRNAs had not yet been described, whereas the second mRNA was highly homologous to a relatively uncharacteristic gene termed pT-2. These results illustrate the utility of the differential display method for isolating and identifying uniquely expressed genes from tissues maintained in the microenvironment where tumors arise naturally.

Animals↗
PubMed1993

Immortalization phenotype dissociated from the preneoplastic phenotype in mouse mammary epithelial outgrowths in vivo.

Mouse mammary epithelial cells (MMEC) isolated from normal virgin BALB/c female mice and grown in cell culture for various lengths of time were injected into the mammary fat pads of syngenic mice. Of the ductal outgrowths which resulted from the injected MMEC, four gave rise to outgrowths that were serially transplanted beyond the lifetime of normal ductal outgrowths. The lifetime of normal ducts is five or six transplant generations. The four ductal outgrowth lines, termed EL for 'extended life', have been serially transplanted for 7, 9, 13 and 14 transplant generations. The outgrowths are predominantly ductal in morphology, do not exhibit intraductal epitheliosis characteristic of ductal hyperplasias, are ovarian dependent for growth and are responsive to prolactin-mediated alveolar differentiation. Three of the EL lines, EL5, 7 and 11 have not produced any tumors spontaneously (0/64) and only one tumor after dimethylbenz[a]anthracene (DMBA) treatment (1/30). The fourth line, EL12, differs from the other three in the presence of a limited degree of alveolar differentiation. The EL12 line has not produced any spontaneous tumors (0/23) but is somewhat more responsive to DMBA (3/10). We interpret the EL lines (at least EL11 and EL12) to represent cell populations where the immortalized phenotype is dissociated from the hyperplastic phenotype which is characteristic of mouse mammary preneoplastic populations. The tumor suppressor gene, p53, is not overexpressed in the EL ductal outgrowths. To our knowledge, this is the first example of cell populations in vivo that are immortalized but otherwise normal. As such, they may represent the earliest stage observable in the genesis of mouse mammary tumors and provide unique cell populations to examine molecular alterations associated with the property of immortality.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Significance of selenium-labeled proteins for selenium's chemopreventive functions.

A 58 kDa selenium-labeled protein purified from mouse mammary epithelial cells (MMEC) was used to examine whether selenium modulates protein synthesis or is just a marker for cellular selenium status. The protein was isolated using Sephadex G150 gel filtration and DEAE-Sephadex A50 ion-exchange chromatography. It was further analysed using 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and was found as a single spot with a pI of 4.6. The immunoreactivity with anti-58 kDa antiserum and the 75Se signal co-localized on a single 58 kDa protein band on both 1D- and 2D-PAGE. Partial amino acid analysis of the peptide showed homology with the thiol protein disulfide oxidoreductase (TPDO). Varying the selenium concentration in culture medium did not affect the protein content or the immunoreactivity of the 58 kDa protein. Additionally, selenium did not seem to regulate the activity of TPDO in TM6 cells. The glutathione peroxidase activity of TM6 cells, taken as the internal positive control, was enhanced with the increase in selenium concentration in the medium. The results suggest that selenium is attached to the 58 kDa protein, but does not regulate either its protein synthesis or its functional activity. We conclude that selenium labeling of the 58 kDa protein reflects the cellular selenium status but probably is not involved in its chemopreventive ability.

Amino Acid Sequence↗
PubMed1993

Immunophenotypic properties and estrogen dependency of budding cell structures in the developing mouse mammary gland.

The initial phase of growth of the parenchymal component of the mouse mammary gland is ductal clongation, which is mainly accomplished by proliferating cells in a specialized structure termed end bud. End buds are composed of multiple layers of epithelial cells (so called body cells) which are capped by a single layer of morphologically unique cells termed cap cells. We sought to examine the interrelationship between cap cells and other epithelial cell subclasses using a variety of antibodies to different keratin proteins and also antibodies to vimentin, actin and collagen IV. An extensive immunohistochemical characterization of the epithelial components of the developing and differentiating mammary gland demonstrated that cap cells were devoid of any immunohistochemically-detectable keratins but were positive for collagen IV. In contrast, the majority of cells in the end bud along with the luminal epithelial and myoepithelial cells were keratin positive. The body cells of the end bud were the only cells which were positive for antibody to keratin 6, a keratin which previously has been reported to be expressed in proliferating mammary epithelial cells. In addition, estrogen receptor was localized only to epithelial cells of ducts, alvcoli and body cells of end buds, but not to cap cells or myoepithelial cells. We interpret these results to suggest that cap cells are not totpotent stem cells but rather cells specialized in paving the way for ductal elongation as well as serving as precursors to myoepithelial cells.

Actins↗
PubMed1993

p53 mutations in mouse mammary epithelial cells: instability in culture and discordant selection of mutations in vitro versus in vivo.

The phenotypes of p53 mutations found in human and murine tumors often are analyzed using a variety of transformation assays in vitro, but data have not been available to correlate in vitro effects with in vivo activities. We have assessed the effects of p53 mutations using mouse mammary epithelial cell lines which can be analyzed both in vitro and in vivo. Parental mammary epithelial cell lines (FSK series) injected into cleared mammary fat pads of syngeneic mice frequently give rise to preneoplastic lesions (HAN) which can be reestablished in culture (TM lines) to permit analysis of genetic changes important in the development of preneoplasia. Characterization of the FSK3 cell line revealed a cell population mixed with respect to p53 genotypes. One subpopulation of mutant (Ser233-234) p53-expressing cells was selected in a preneoplastic mammary outgrowth in vivo (TM3), whereas another minor population of mutant (Pro135) p53-expressing cells was selected during culturing of FSK3 cells in vitro. When FSK3 cells were subdivided and passaged in parallel in vitro, p53 genotypes continued to evolve and diverge. These findings reveal that selective pressures exerted on mammary epithelial cell populations in vivo are different from pressures present in vitro. Selective forces may vary from one cell culture environment to another. The growth advantage conferred by a specific p53 mutation appears to differ in vivo versus in vitro. We propose that caution should be exercised when attempting to correlate the effects of p53 mutations assayed in cell culture systems with the in situ phenotypes of mutant p53 in cancer.

Amino Acid Sequence↗
PubMed1992

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.

Animals↗