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Tesi etd-02142011-132621


Tipo di tesi
Tesi di dottorato di ricerca
Autore
AL HAMAD, MOHAMMAD
URN
etd-02142011-132621
Titolo
The Pathogenic Role of the Human Mammary Tumor Virus (HMTV) in Human Breast Cancer
Settore scientifico disciplinare
MED/08
Corso di studi
ONCOLOGIA SPERIMENTALE E MOLECOLARE
Commissione
tutor Bevilacqua, Generoso
tutor Dott.ssa Mazzanti, Chiara Maria
Parole chiave
  • Breast Cancer
  • HMTV
Data inizio appello
22/03/2011;
Disponibilità
completa
Riassunto analitico
ABSTRACT

A viral etiology of human breast cancer has been postulated for decades after the identification of MMTV (Murine Mammary Tumor Virus). The detection of HMTV (Human Mammary Tumor Virus) env exogenous sequences in 30-40% of invasive breast carcinoma increased the interest towards this hypothesis. To look for HMTV env exogenous sequences during cancer progression could contribute to a better understanding of their role in breast cancer. This work analyzes the presence of HMTV env exogenous sequences in the first phases of carcinogenesis, i.e. the pre-invasive, as well as in metastatic lesions.
Formalin fixed and paraffin embedded samples were utilized: 20 Usual type Ductal Hyperplasia (UDH), 22 Atypical Ductal Hyperplasia (AH), 49 Ductal Carcinoma In Situ (DCIS), 20 Infiltrative Ductal Carcinoma (IDC), 26 Normal Epithelial Cells (NEC) collateral to DCIS or IDC, i.e. present in the same histological section, 22 primary breast cancers and their respective non metastatic lymph nodes, 23 primary breast cancers and their metastatic lymph nodes. As a negative control we used reductive mammoplasties, thyroid and colon carcinoma, and blood of healthy donors. All samples were laser microdissected. Fluorescent nested - PCR was used to detect the presence of HMTV env exogenous sequences. Generated fluorescent amplicons were sized on an automatic DNA sequencer. DNA extracted from tissues of 9 patients was analyzed by quantitative RT-PCR. Moreover, we created primary cell line of human breast cancer that was positive for HMTV env exogenous sequences, and then we treated the cells with 106 M Dexamethasone. HMTV env exogenous sequences were found in 19% of NEC collateral to DCIS or IDC, 27% of AH, 80% of DCIS, 35% of IDC, primary breast cancer cases that do not develop metastasis 50%, their respective lymphocytes 36%, primary breast cancers that develop metastasis 69.5%, and their metastatic cancer in lymph nodes 68.4%. Controls results were negative. RT-PCR and CISH confirmed these results. The expression of HMTV in primary breast cancer cell line was started to increase after 16 days of treatment with Dexamethasone. These data could contribute to understanding the meaning of the presence of HMTV in breast carcinogenesis.
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